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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. By using the sucrose gap technique, we have investigated the effect of the metabolically stable P2Y receptor agonist, adenosine 5'-O-2-thiodiphosphate (ADPbetaS), on the membrane potential and tension in the circular muscle of the guinea-pig proximal colon. All experiments were performed in the presence of atropine (1 microM), guanethidine (3 microM), indomethacin (3 microM), nifedipine (1 microM), L-nitroarginine (L-NOARG, 100 microM) and of the tachykinin NK1 and NK2 receptor antagonists, SR 140333 (0.1 microM) and GR 94800 (0.1 microM), respectively. 2. ADPbetaS (100 microM for 15 s) evoked a tetrodotoxin- (1 microM) resistant hyperpolarization and contraction of the smooth muscle. In the presence of apamin (0.1 microM), the ADPbetaS-induced hyperpolarization was converted to depolarization and the contraction was potentiated while tetraethylammonium (TEA, 10 mM) did not affect significantly the response to ADPbetaS. The combined application of apamin and TEA reproduced the effect observed with apamin alone. 3. Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acids (PPADS, 30 microM) slightly but significantly increased the ADPbetaS-induced hyperpolarization, while the contraction evoked by ADPbetaS was reduced by about 80%. Suramin (100 microM) did not affect the ADPbetaS-induced hyperpolarization but totally blocked the ADPbetaS-induced contraction. In the presence of suramin (100 microM), a small relaxation of the circular muscle was observed upon application of ADPbetaS. 4. The contraction and hyperpolarization evoked by ADPbetaS were abolished in Ca2+-free Krebs solution. The blocker of sarcoplasmic reticulum Ca2+ pump, cyclopiazonic acid (10 microM) reduced contraction and hyperpolarization induced by ADPbetaS by about 60 and 50%, respectively. 5. A comparison of our present and previous findings enables to conclude that at least 3 types of P2 receptors are present on the smooth muscle of the guinea-pig colon, as follows: (1) inhibitory P2 receptors, producing an apamin-sensitive hyperpolarization, which are activated by alpha,beta-methylene ATP (alpha,beta-meATP) and by endogenously released purines, sensitive to suramin and PPADS; (2) inhibitory P2 receptors, producing an apamin-sensitive hyperpolarization, which are activated by ADPbetaS and are resistant to suramin and PPADS; (3) excitatory P2 receptors, producing contraction, which are activated by ADPbetaS and are sensitive to suramin and PPADS. The data also support the idea of the existence of a restricted pool of specialized junctional P2 receptors producing the apamin-sensitive NANC inhibitory junction potential in response to endogenous ligand(s).
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PMID:Pharmacological evidence for the existence of multiple P2 receptors in the circular muscle of guinea-pig colon. 948 62

The purpose of this study was to investigate the contribution of adenosine-5'-triphosphate (ATP) to segmental (L6-S2) spinal electrical stimulation evoked increases in intra-vesical pressure in pithed rats. Exogenous ATP and substance P produced dose-dependent increases in intra-vesical pressure (ED10 mmHg (dose required to elicit 10 mmHg increase in intra-vesical pressure)= 1.7 mg/kg and 1.1 microg/kg, i.v., respectively). Desensitisation (or antagonism) of P2x purinoceptors with alpha,beta-methylene ATP (alpha,beta-meATP; 30 microg/kg per min, i.v.) or pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 10 mg/kg, i.v.) significantly (p < 0.05) antagonized the intra-vesical pressure responses to ATP (> 8 and 3.6-fold increase in ED10 mmHg, respectively) but had no significant effect on intra-vesical pressure responses to substance P. Spinal stimulation evoked frequency-dependent increases in intra-vesical pressure (EF20 mmHg (frequency required to produce 20 mmHg increase in intra-vesical pressure) = 3.4 Hz). Blockade of muscarinic cholinoceptors and adrenoceptors with atropine (3 mg/kg, i.v.), propranolol (3 mg/kg, i.v.) and phentolamine (10 mg/kg, i.v.) produced marginal attenuation of the intra-vesical pressure responses to spinal stimulation indicating a major non-adrenergic non-cholinergic (NANC) component in the overall response. The NANC responses were significantly (p < 0.05) antagonized by alpha,beta-meATP (30 microg/kg per min, i.v.) and PPADS (10 mg/kg, i.v.) (> 2.6-fold increase in EF20 mmHg), consistent with involvement of a purinergic neurotransmitter, presumably ATP. Comparative studies in young (4-6 months) and old (21-23 months) Fischer rats revealed no age-dependent changes in the relative contribution of the cholinergic and purinergic systems, with the latter being the dominant one. These findings suggest that purinergic neurotransmission, presumably mediated by ATP acting via P2x purinoceptors, represents a major component of excitatory innervation to the urinary bladder in pithed rats.
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PMID:Evidence for purinergic neurotransmission in the urinary bladder of pithed rats. 966 99

Application of electrical field stimulation (EFS; trains of 10 Hz, 0.25 ms pulse width, supramaximal voltage for 60 s) to the guinea-pig isolated common bile duct pretreated with atropine (1 microM), produced a slowly-developing contraction ('on' response) followed by a quick phasic 'off' contraction ('off peak' response) and a tonic response ('off late' response), averaging 16+/-2, 73+/-3 and 20+/-4% of the maximal contraction to KCl (80 mM), n=20 each, respectively. Tetrodotoxin (1 microM; 15 min before) abolished the overall response to EFS (n 8). Neither in vitro capsaicin pretreatment (10 microM for 15 min), nor guanethidine (3 microM, 60 min before) affected the excitatory response to EFS (n 5 each), showing that neither primary sensory neurons, nor sympathetic nerves were involved. Nomega-nitro-L-arginine (L-NOARG, 100 microM, 60 min before) or naloxone (10 microM, 30 min before) significantly enhanced the 'on' response (294+/-56 and 205+/-25% increase, respectively; n=6-8, P<0.01) to EFS. The combined administration of L-NOARG and naloxone produced additive enhancing effects (655+/-90% increase of the 'on' component, n = 6, P<0.05). The tachykinin NK2 receptor-selective antagonist MEN 11420 (1 microM) almost abolished both the 'on' and 'off late' responses (P<0.01: n=5 each) to EFS, and reduced the 'off-peak' contraction by 55+/-8% (n=5, P<0.01). The subsequent administration of the tachykinin NK1 receptor-selective antagonist GR 82334 (1 microM) and of the tachykinin NK3 receptor-selective antagonist SR 142801 (30 nM), in the presence of MEN 11420 (1 microM), did not produce any further inhibition of the response to EFS (P>0.05; n=5 each). At 3 microM, GR 82334 significantly reduced (by 68+/-9%, P<0.05, n=6) the 'on' response to EFS. The contractile 'off peak' response to EFS observed in the presence of both MEN 11420 and GR 82334 (3 microM each) was abolished (P<0.01; n=6) by the administration of the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 microM). PPADS (30 microM) selectively blocked (75+/-9 and 50+/-7% inhibition, n = 4 each) the contractile responses produced by 100 and 300 microM ATP. Tachykinin-containing nerve fibres were detected by using immunohistochemical techniques in all parts of the bile duct, being distributed to the muscle layer and lamina propria of mucosa. In the terminal part of the duct (ampulla) some labelled ganglion cells were observed. In conclusion, this study shows that in the guinea-pig terminal biliary tract tachykinins, released from intrinsic neuronal elements, are the main NANC excitatory neurotransmitters, which act by stimulating tachykinin NK2 (and possibly NK1) receptors. ATP is also involved as excitatory neurotransmitter. Nitric oxide and opioids act as inhibitory mediators/modulators in this preparation.
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PMID:Evidence that tachykinins are the main NANC excitatory neurotransmitters in the guinea-pig common bile duct. 975 87

In functional experiments, we have investigated the effect exerted by neurotransmitters released from capsaicin-sensitive primary afferent nerve terminals in the isolated guinea-pig common bile duct. In resting preparations, capsaicin (0.1 microM) produced a quick contraction (45.1+/-4% of KCl 80mM) which was abolished by either atropine (1 microM) or tetrodotoxin (0.5 microM). The tachykinin receptor-selective antagonists GR 82334 (NK1 receptor-selective; 3 microM), MEN 11420 (NK2 receptor-selective; 1 microM) and SR 142801 (NK3 receptor-selective; 0.1 microM) administered separately failed to reduce the capsaicin-evoked contraction, whereas any combination of the three antagonists was effective: GR 82334 plus MEN 11420, 36+/-7% reduction; GR 82334 plus SR 142801, 48+/-4% reduction; MEN 11420 plus SR 142801, 55+/-3% reduction; GR 82334 plus MEN 11420 plus SR 142801, 57+/-5% reduction. Neither the CGRP1 receptor antagonist h-CGRP (8-37) (1.5 microM) nor the P2X purinoceptor antagonist PPADS (50 microM) affected the contractile response to capsaicin. The effect of capsaicin (0.1 microM) was abolished by pretreatment with capsaicin itself (10 microM for 15 min). Human calcitonin gene-related peptide (h-CGRP; 0.1 microM) mimicked the effect of capsaicin on resting preparations (contractile response =28% of KCl 80 mM). In preparations precontracted with a submaximal concentration of KCl (24 mM), and in the presence of atropine (1 microM), GR 82334 (3 microM) and MEN 11420 (3 microM), capsaicin (1 microM) produced a tetrodotoxin-insensitive long-lasting relaxation (45+/-3% reduction of tone, at 4min from administration), which was unaffected by the nitric oxide (NO) synthase inhibitor, L-NOARG (100 microM). h-CGRP (10-50 nM) produced a similar sustained relaxation of precontracted preparations (59+/-4% reduction of tone). h-CGRP (8-37) (1.5 microM) almost completely reversed the relaxations produced by both capsaicin and h-CGRP. Application of electrical field stimulation (EFS: trains of stimuli of 10Hz; 0.25ms pulse width; supramaximal voltage; for 60s) to precontracted preparations produced a sustained, tetrodotoxin (1 microM)-sensitive relaxation (32+/-4% reduction of tone). L-NOARG (100 microM) greatly reduced (69+/-5% inhibition) the EFS-elicited relaxation. A complete reversal of the relaxant response to EFS into a contraction was obtained by administering L-NOARG to preparations in which a functional blockade of capsaicin-sensitive primary afferent neurons had been achieved by incubating the tissue with capsaicin (10 microM) for 15 min. At immunohistochemistry, tachykinin- and CGRP-immunoreactivities (TK-IR/CGRP-IR) were detected in varicose nerve fibers throughout the common bile duct, while TK-IR cell bodies were observed in the terminal portion (ampulla) only. In vivo pretreatment with capsaicin (50 mg/kg; 6-7 days before) decreased the number of CGRP-IR nerves, whereas the TK-IR neural network was apparently unchanged. In conclusion, our data provide functional evidence for the presence of capsaicin-sensitive primary afferent nerve endings in the guinea-pig terminal biliary tract, whose stimulation by capsaicin or EFS produces the release of tachykinins and CGRP. In addition, morphological evidence is provided that the bulk of TK-IR material in the biliary tract is contained in intrinsic neuronal elements, while CGRP in this tissue is of extrinsic origin only. Tachykinins, probably released in small amounts by capsaicin, act by activating receptors of the NK1, NK2 and NK3 type, most probably located on intrinsic cholinergic neurons, which in turn release ACh to produce the final excitatory motor response. The contractile response to capsaicin obtained in the presence of the three tachykinin receptor antagonists could be due to the co-released CGRP and/or to other unknown neurotransmitters. CGRP produces either indirect excitatory or direct inhibitory responses by stimulation of CGRP2 and CGRP1 receptors, respectively.
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PMID:Involvement of endogenous tachykinins and CGRP in the motor responses produced by capsaicin in the guinea-pig common bile duct. 1054 38

The contractile effect of capsaicin in the guinea-pig small intestine involves an activation of enteric cholinergic neurons. Our present data show that the P(2) purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 30 microM) significantly reduces the contractile response to capsaicin (2 microM) in the presence, but not in the absence, of the tachykinin receptor antagonists [O-Pro(9), (Spiro-gamma-lactam)Leu(10), Trp(11)]physalaemin (1-11) (GR 82334; 3 microM) and (S)-(N)-(1-(3-(1-benzoyl-3-(3, 4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylpiperidine-4-yl)-N -methylacetamide (SR 142804: 100 nM) (for blocking tachykinin NK1 and NK3 receptors, respectively). PPADS (30 microM) fails to influence submaximal cholinergic contractions evoked by cholecystokinin octapeptide (CCK-8; 2-3 nM) or senktide (1 nM), or the direct smooth muscle-contracting effect of histamine (100-200 nM). A higher concentration (300 microM) of PPADS is also without effect against the stimulatory action of cholecystokinin octapeptide. This means that PPADS can probably be safely used as a purinoceptor antagonist in intestinal preparations. The putative pituitary adenylate cyclase activating peptide (PACAP) receptor antagonist PACAP-(6-38) (3 microM) significantly reduces the contractile effect of PACAP-(1-38) (10 nM) and abolishes that of vasoactive intestinal polypeptide (VIP; 10 nM). PACAP-(6-38) (3 microM) fails to influence the effect of capsaicin (2 microM) both in the absence and in the presence of tachykinin receptor antagonists. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NOARG; 100 microM) also fails to inhibit the capsaicin-induced motor response. We conclude that an endogenous ligand of PPADS-sensitive P(2) purinoceptors (possibly ATP), but not a VIP/PACAP-like peptide or NO, is involved in the nontachykininergic activation of cholinergic neurons in the course of the capsaicin-induced contraction.
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PMID:Evidence for the involvement of ATP, but not of VIP/PACAP or nitric oxide, in the excitatory effect of capsaicin in the small intestine. 1076 72

The effect of the pituitary adenylate cyclase activating polypeptide (PACAP) receptor antagonist PACAP(6-38) on the relaxant response to exogenous PACAP, vasoactive intestinal polypeptide (VIP) and nonadrenergic, non-cholinergic (NANC) nerve stimulation was tested in the guinea-pig taenia caeci, in the presence of atropine (10(-6) M) and guanethidine (3x10(-6) M). PACAP(6-38) (3x10(-6) M) strongly inhibited sub-maximal relaxations evoked by exogenous PACAP (1-3x 10(-8) M) or VIP (10(-8) M), but not those due to isoprenaline (4-8x10(-8) M) or ATP (10(-6) M). PACAP(6-38) caused a small but significant (approximately 20%) inhibition of the NANC relaxation due to electrical field stimulation (1 Hz or 10 Hz for 20 s). At these frequencies PACAP(6-38) caused no inhibition of the NANC relaxation in the presence of the P2 purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 5x10(-5) M), or PPADS plus the NO-synthase blocker NG-nitro-L-arginine (L-NOARG; 10(-4) M); in preparations pretreated with L-NOARG (10(-4) M) alone PACAP(6-38) retained its inhibitory effect. The PPADS- and L-NOARG-resistant NANC relaxation with 10 Hz electrical stimulation was blocked by apamin (10(-7) M); it was not significantly modified by the tachykinin receptor antagonist spantide (10(-5) M). Tachyphylaxis to PACAP(1-27) (10(-7) M for 10 min) strongly inhibited the relaxation due to PACAP(1-38) (1-3x10(-8) M) and reduced electrical stimulation-evoked relaxations by half. The putative VIP antagonist VIP(10-28) (10(-5) M) failed to significantly reduce the relaxant action of exogenous VIP (1-3x10(-8) M). Relaxation induced by PACAP(1-38) (1-2x10(-8) M) was not influenced by a mixture of PPADS (5x10(-5) M) and L-NOARG (10(-4) M). It is concluded that: (a) PACAP(6-38) is a VIP/PACAP antagonist in the guinea-pig taenia caeci; (b) a release of a VIP/PACAP-like substance from enteric nerves is involved in the NANC relaxation in this preparation, but its contribution is relatively small and seems to depend on the functional integrity of the PPADS-sensitive inhibitory mechanism; (c) the PPADS- plus L-NOARG-resistant NANC relaxation probably involves apamin-sensitive K+ channels.
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PMID:Inhibitory effect of PACAP(6-38) on relaxations induced by PACAP, VIP and non-adrenergic, non-cholinergic nerve stimulation in the guinea-pig taenia caeci. 1083 2

In this study we have characterized the role of sensory fibers and of the sensory peptides, neurokinin A (NKA) and calcitonin gene-related peptide (CGRP), on the contractile responses evoked by single pulse electrical field stimulation (EFS) in the hamster urinary bladder. EFS of the hamster isolated urinary bladder produced twitch contractions which were unaffected by atropine but abolished by tetrodotoxin. The P2 purinoreceptor antagonist PPADS (30 microM) inhibited twitches by 66+/-4% on its own and by 78+/-3% in the presence of atropine. The selective tachykinin NK2 receptor antagonist nepadutant produced a slight but consistent reduction of twitch amplitude (-21+/-3%) at 1 microM. Addition of nepadutant to atropine and PPADS did not further increase their inhibitory effect. The application of hCGRP (10-300 nM) produced a concentration-dependent inhibition of twitches (Emax -38+/-3%, EC50=12 nM) and a small reduction of tone (0.5+/-0.09 mN). Similar effects were obtained with capsaicin (0.1-10 microM) which inhibited EFS-evoked contractions with an EC50 of 100.0 nM and a maximal effect of 34+/-4% inhibition at 1 microM. Under submaximal parameters of stimulation NKA (10 nM) increased the amplitude of twitches by 45+/-6% and produced a concentration-dependent tonic contraction (EC50=55.9 nM). The CGRP1 receptor subtype antagonist, hCGRP(8-37), increased by 29+/-8% the EFS-evoked contractions and significantly reduced the response to 0.1 microM CGRP. Capsaicin (10 microM) increased both CGRP-LI and NKA-LI release from superfused slices of hamster urinary bladder by about sixfold and by about 70%, over baseline, respectively. A second application of capsaicin was ineffective, indicating a complete desensitization of sensory nerve efferent function. In the hamster urinary bladder the sensory neuropeptides NKA and CGRP are co-released by sensory fibers after stimulation either by EFS or capsaicin. However, the role of CGRP appears functionally predominant.
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PMID:The role of sensory neuropeptides in motor innervation of the hamster isolated urinary bladder. 1152 Nov 67

We investigated the receptor-mediated regulation of nifedipine-insensitive, high voltage-activated Ca(2+) currents in guinea-pig terminal mesenteric arterioles (I(mVDCC)) using the whole-cell clamp technique. Screening of various vasoactive substances revealed that ATP, histamine and substance P exert modulatory effects on I(mVDCC). The effects of ATP on I(mVDCC) after complete P2X receptor desensitization exhibited a complex concentration dependence. With 5 mM Ba(2+), ATP potentiated I(mVDCC) at low concentrations (approximately 1-100 microM), but inhibited it at higher concentrations (>100 microM). The potentiating effects of ATP were abolished by suramin (100 microM) and PPADS (10 microM) and by intracellular application of GDPbetaS (500 microM), whereas a substantial part of I(mVDCC) inhibition by milimolar concentrations of ATP remained unaffected; due probably to its divalent cation chelating actions. In divalent cation-free solution, I(mVDCC) was enlarged and underwent biphasic effects by ATPgammaS and ADP, while 2-methylthio ATP (2MeSATP) exerted only inhibition, and pyrimidines such as UTP and UDP were ineffective. ATP-induced I(mVDCC) potentiation was selectively inhibited by anti-Galpha(s) antibodies or protein kinase A (PKA) inhibitory peptides and mimicked by dibutyryl cAMP. In contrast, ATP-induced inhibition was selectively inhibited by Galpha(q/11) antibodies or protein kinase C (PKC) inhibitory peptides and mimicked by PDBu. Pretreatment with pertussis toxin was ineffective. The apparent efficacy for I(mVDCC) potentiation with PKC inhibitors was: ATPgammaS > ATP>/=ADP and for inhibition with PKA inhibitors was: 2MeSATP > ATPgammaS > ATP > ADP. Neither I(mVDCC) potentiation nor inhibition showed voltage dependence. These results suggest that I(mVDCC) is multi-phasically regulated by external ATP via P2Y(11)-resembling receptor/G(s)/PKA pathway, P2Y(1)-like receptor/G(q/11)/PKC pathway, and metal chelation.
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PMID:Multiple regulation by external ATP of nifedipine-insensitive, high voltage-activated Ca(2+) current in guinea-pig mesenteric terminal arteriole. 1189 51

Simultaneous intracellular recordings were made from pairs of circular muscle (CM) cells, at the oral and anal ends of a segment of guinea-pig distal colon, to investigate the neuronal mechanisms underlying faecal pellet propulsion. When a minimum degree of circumferential stretch was applied to sheet preparations of colon, recordings from CM cells revealed either no ongoing junction potentials, or alternatively, small potentials usually < 5 mV in amplitude. Maintained circumferential stretch applied to these preparations evoked an ongoing discharge of excitatory junction potentials (EJPs) at the oral recording site (range: 1-25 mV), which lasted for up to 6 h. The onset of each large oral EJP was time-locked with the onset of an inhibitory junction potential (IJP) at an anal recording electrode, located 2 cm from the oral recording. Similar results were obtained in isolated intact tube preparations of colon, when recordings were made immediately oral and anal of an artificial faecal pellet. The amplitudes of many large (> 5 mV) oral EJPs were linearly related to the amplitudes of anal IJPs occurring 20 mm apart. In the absence of an L-type Ca(2+) channel blocker, action potentials occurred on each large oral EJP. Synchronized discharges of stretch-activated EJPs and IJPs were preserved following pretreatment with capsaicin (10 microM), were unaffected by nifedipine (1 microM) and did not require the mucosa or submucous plexus. EJPs and IJPs were abolished by hexamethonium (300 microM) or tetrodotoxin (1 microM), but persisted in the presence of pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10 microM) or an NK(3) tachykinin receptor antagonist (Neurokinin A 4-10; 100 nM to 5 microM). In summary, maintained circumferential stretch of the distal colon activates a population of intrinsic mechanosensory neurons that generate repetitive firing of ascending excitatory and descending inhibitory pathways to CM. These mechanosensory neurons, which may be interneurons, are stretch sensitive, rather than muscle tension sensitive, since they are resistant to muscular paralysis. We suggest the synchrony in onset of oral EJPs and anal IJPs over large regions of colon is due to synchronous synaptic activation of ascending and descending interneurons.
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PMID:A rhythmic motor pattern activated by circumferential stretch in guinea-pig distal colon. 1245 39

An attempt has been made to pharmacologically isolate cholinergic, P(2) purinoceptor-mediated and peptidergic (capsaicin-sensitive, tachykinin-mediated) contraction of the guanethidine-treated rat bladder detrusor preparation, in vitro. The effect of experimental diabetes was assessed on these types of contraction. Responses were evoked by electrical field stimulation (single shocks or 1 Hz for 30 s or 10 Hz for 40 s). Single shocks and 1-Hz stimulation were applied in the presence of (a). atropine (1 microM) or (b). P(2) purinoceptor antagonists (50 microM pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) [PPADS] plus 100 microM suramin. Long-term electrical field stimulation (10 Hz for 40 s) (c). was applied with both atropine and the P(2) purinoceptor antagonists present in the organ bath. The effects of capsaicin (d). and ATP (e). were also studied. Three groups of experimental animals were used: streptozotocin-treated (50 mg.kg(-1) i.p., 8 weeks before the experiment), parallel solvent-treated and untreated rats. (a). Responses to electrical field stimulation in the presence of atropine were reduced by half by PPADS plus suramin, but were resistant to capsaicin tachyphylaxis. They were enhanced in preparations taken from diabetic rats. (b). Contractions to electrical field stimulation in the presence of PPADS plus suramin were reduced by 2/3 by atropine, but were left unchanged by capsaicin or diabetes. (c). Contractions to long-term stimulation had a quick and a sustained phase. Especially the latter was inhibited by capsaicin tachypyhlaxis; it was also strongly reduced in preparations taken from diabetic rats. (d). Contractions to capsaicin (30 nM and 1 microM) were resistant to tetrodotoxin, strongly reduced by a combination of tachykinin NK(1) and NK(2) receptor antagonists, and slightly reduced in preparations from diabetic animals. Capsaicin (1 microM) had no acute inhibitory action on cholinergic or purinergic responses, nor did it cause relaxation in precontracted preparations treated with tachykinin receptor antagonists. (e) ATP-induced contractions were strongly reduced by PPADS plus suramin (50 plus 100 microM) and to a similar degree by 100 plus 200 microM, respectively. It is concluded that experimental diabetes selectively impairs peptidergic, capsaicin-sensitive responses (especially those that involve impulse conduction) in the rat detrusor preparation. The contractile response to electrical field stimulation that remains after atropine plus the P(2) purinoceptor antagonists has a yet unknown transmitter background.
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PMID:Effect of experimental diabetes on cholinergic, purinergic and peptidergic motor responses of the isolated rat bladder to electrical field stimulation or capsaicin. 1455 87


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