Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Supramaximal repetitive field stimulation with pulses of 50 microseconds produced contraction of strips of bladder from rabbits and guinea-pigs. Atropine reduced responses at all frequencies to about 60% and the contraction was poorly maintained. With the double sucrose-gap technique large excitatory junction potentials (e.j.p.s) were recorded with superimposed action potentials. These were not reduced by atropine or phentolamine. Substance P (SP) produced contraction and increased the frequency of spontaneous action potentials recorded with micro-electrodes from bladder strips. Vasoactive intestinal peptide (VIP) produced relaxation and slowed action potentials in rabbit but had no effect in guinea-pig; neurotensin, somatostatin and leu-enkephalin were without action in either species. When the tissue was kept in contact with SP, a second application after 10 min produced only a small contraction suggesting that SP receptors were desensitized. However, the electrical response to field stimulation was unchanged and the mechanical response was increased. Chymotrypsin reduced mechanical responses to SP but had no effect on responses to field stimulation. The SP analogue, D-Pro2, D-Phe7, D-Trp9-SP, had no effect on responses to SP or to field stimulation. It is concluded that the bladder receives excitatory non-cholinergic innervation which is responsible for a large excitatory junction potential and contraction. Although SP can contract the detrusor muscle, it is unlikely that it is an excitatory transmitter or that any of the five peptides act as modulators of transmitter release.
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PMID:Non-cholinergic neurotransmission and the effects of peptides on the urinary bladder of guinea-pigs and rabbits. 242

The influence of alpha-chymotrypsin and diazepam on the phasic (mainly direct) and tonic (indirect, probably substance P-mediated) components of intestinal cholinergic contractions, induced by the GABA-A receptor agonist 3-aminopropane sulphonic acid (3-APS), was investigated in the guinea-pig ileum. alpha-Chymotrypsin, at a concentration (20 U/ml) not affecting submaximal Ach (0.1 microM) contractions, preferentially depressed the tonic component of the 3-APS (30 microM)-induced response. A brief exposure (10 or 60 sec) to diazepam (0.1 microM) potentiated both the phasic and the tonic contractions evoked by low (10, 30 microM) 3-APS concentrations. This potentiation was prevented by bicuculline (30 microM), hyoscine (1 microM) and flumazenil (1, 3 microM). These results provide further support for an involvement of a peptide neurotransmitter on GABA-A receptor-mediated cholinergic response in the ileum. The modulation of this response by diazepam is probably exerted through recognition sites resembling the "central type" benzodiazepine receptors.
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PMID:Cholinergic contractions induced by GABA-A receptor activation in the guinea-pig ileum are inhibited by alpha-chymotrypsin and potentiated by diazepam. 285 13

1. An enzyme which can be extracted from brain inactivates nerveside in the optimum pH range 5.8-7.0.2. The polybasic acids trypan blue and its analogue trypan red, bromphenol blue and its analogue bromthymol blue at concentrations of 0.22 mM and ethylenediaminetetra-acetic acid (EDTA) at a concentration of 1 mM are strong inhibitors of the enzyme.3. Penicillin which is a monobasic carboxylic acid also inhibits the enzyme but only if concentrations as high as 3.6 mM are used. The antibiotic streptomycin which is a basic substance does not inhibit the enzyme.4. Caffeine at a concentration of 7.2 mM only weakly inhibits the enzyme.5. Chymotrypsin and wheat germ acid phosphatase also inactivate nerveside at pH 5.9 and are inhibited by the acidic dyes and penicillin. EDTA inhibits wheat germ phosphatase but activates chymotrypsin.6. Inactivation of nerveside by the brain enzyme and by wheat germ phosphatase is different from the action of chymotrypsin. Nerveside solutions incubated with chymotrypsin completely lose all biological activity whereas if incubation is carried out with either the brain enzyme or wheat germ acid phosphatase a residual biological activity remains even when the concentration of these two enzymes is increased. This residual biological activity is due to a peptide as it is destroyed by chymotrypsin.7. The manner in which nerveside is inactivated by the brain enzyme is uncertain as the preparation of the latter contained phosphodiesterase and protease activities which were similarly inhibited by the acid dyes, penicillin and EDTA.8. Pentylenetetrazole, picrotoxin, strychnine and tetanus toxin do not inhibit the brain enzyme.9. The nerveside-inactivating enzyme is not identical with the Substance P-inactivating enzyme in brain as the former is inhibited by EDTA while the latter is not.
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PMID:The inhibitory effect of convulsant agents on the enzyme in brain which inactivates nerveside. 439 Mar 85

1. Intracellular recordings were made from neurones in the myenteric plexus of the ileum isolated from adult guinea-pigs.2. Three synaptic potentials were evoked in different myenteric neurones by focal stimulation of the ganglion surface at a distance of up to 100 mum from the cell body from which the recording was made. These were the fast cholinergic excitatory post-synaptic potential (e.p.s.p.), the slow e.p.s.p. and the slow inhibitory post-synaptic potential (i.p.s.p.).3. 5-hydroxytryptamine and substance P were applied to the neurones by superfusion (10 nm-1 mum) or by electrophoresis within 5 mum of the neurone cell body. 5-HT depolarized, hyperpolarized or had no effect on approximately equal numbers of neurones, whereas substance P depolarized 90% of neurones.4. Many neurones with a depolarizing slow e.p.s.p. were hyperpolarized by superfusion or electrophoretic application of 5-HT.5. Superfusion with 5-HT reversibly depressed the fast e.p.s.p., slow e.p.s.p. and slow i.p.s.p. Superfusion with substance P depressed the slow e.p.s.p.6. Methysergide (10-30 mum) reduced the amplitude of the fast e.p.s.p., the slow e.p.s.p. and the slow i.p.s.p.7. Chymotrypsin (200 mug/ml.) reversibly reduced the amplitude of the slow e.p.s.p., but had no effect on membrane potential, the action potential or the fast e.p.s.p. Chymotrypsin reduced or abolished the depolarization caused by electrophoretic application of substance P, but had no effect on the depolarization or hyperpolarization caused by 5HT.8. The results provide evidence that 5-HT is not the transmitter which mediates the slow e.p.s.p. in myenteric neurones. The slow e.p.s.p. may be caused by substance P or another similar peptide.
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PMID:Mediators of slow synaptic potentials in the myenteric plexus of the guinea-pig ileum. 617 83

Action potentials were recorded simultaneously from the longitudinal and circular muscle layers of the guinea pig isolated small intestine. Both the graded reflex of the longitudinal muscle and the peristaltic reflex proper could be evoked by raising the intraluminal pressure. At low intraluminal pressures, intervals between spike bursts of the circular muscle were longer than those of the longitudinal muscle. The higher the intraluminal pressure, the shorter became the intervals between spike bursts in the circular muscle, until both muscle layers showed synchronous discharge of action potentials. Tetrodotoxin (100 nM) abolished the excitation of both circular and longitudinal muscles produced by raising intraluminal pressure. Hexamethonium (280 microM) abolished excitation of the circular muscle but not that of the longitudinal muscle. Atropine (100 nM) reduced the excitatory effects of raising pressure on both muscle layers but did not abolish them. The atropine-resistant excitation of the circular, but not the longitudinal, muscle was reversibly blocked by exposure to substance P (100-500 nM). Chymotrypsin (200 micrograms/ml) reversibly abolished the atropine-resistant excitation of the circular muscle. It was concluded that during peristalsis both longitudinal and circular muscle layers are activated synchronously; muscle activation during peristalsis is not entirely cholinergic but may involve in addition a substance P-like peptide.
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PMID:Electrical activity of longitudinal and circular muscle during peristalsis. 618 7

The nature of the inhibitory transmitter in the canine gastric muscularis mucosae was studied in vitro using superfusion techniques. The inhibitory effect of nerve stimulation (10 V, 200 mus, 10 Hz) was not altered by adrenergic, cholinergic or serotonergic antagonists. Adenosine triphosphate had no effect on spontaneous mechanical activity. Nucleotide pyrophosphatase and apamin had no effect on the response to nerve stimulation. Alpha-chymotrypsin abolished the inhibitory effect of nerve stimulation. Radioimmunoassay of the muscle indicated the presence of gastrin/cholecystokinin-substance P- and vasoactive intestinal polypeptide (VIP)-like immunoreactivity. Of the three peptides present, only VIP produced a concentration-dependent relaxation. A substance with VIP-like immunoreactivity was released during nerve-induced relaxation of the muscle, and its release was blocked by tetrodotoxin and calcium-depleted solution. The inhibitory effect of nerve stimulation was abolished by VIP antiserum. These data strongly support the hypothesis that VIP or a closely related peptide is an inhibitory neurotransmitter in the canine gastric muscularis mucosae.
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PMID:Vasoactive intestinal polypeptide: a putative transmitter in the canine gastric muscularis mucosa. 619 89

1. We investigated the effect of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the peptidase alpha-chymotrypsin on non-adrenergic, non-cholinergic (NANC neural) bronchoconstriction induced by electrical stimulation of the vagus nerves and by capsaicin in anaesthetized guinea-pigs in vivo using pulmonary insufflation pressure (PIP) as an index of bronchial tone. We also investigated the contribution of soluble guanylyl cyclase (SGC) to NANC neural relaxant mechanisms. 2. In the presence of atropine and propranolol, electrical stimulation of the vagus nerves induced a frequency-dependent increase in PIP above baseline of 67% at 2.5 Hz, of 128% at 5 Hz and of 230% at 10 Hz. L-NAME (1-50 mg kg-1, i.v.), at doses inducing increases in systemic blood pressure, dose-relatedly potentiated NANC bronchoconstriction. At 10 mg kg-1 i.v., L-NAME significantly (P < 0.05) potentiated NANC bronchoconstriction by a further 106% at 2.5 Hz and a further 147% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. L-NAME did not induce bronchoconstriction in sham-stimulated control animals. D-NAME did not potentiate NANC bronchoconstriction. Raising systemic blood pressure with phenylephrine did not potentiate vagally-induced bronchoconstriction (2.5 Hz). 3. The NO precursor L-arginine, but not D-arginine, (100 mg kg-1, i.v.) significantly reversed the potentiation by L-NAME of NANC bronchoconstriction. L-Arginine alone significantly inhibited neurogenic bronchoconstriction at 10 Hz (by 74%); the inhibition of 25% at 2.5 Hz was not significant. 4. L-NAME did not significantly affect the increases in PIP induced by intravenous substance P. neurokinin A (NKA) or capsaicin. 5. The inhibitor of SGC, methylene blue (10 mg kg', i.v.) potentiated (by 110-140%) NANC neural bronchoconstriction induced by lower frequencies of nerve stimulation and reversed the reduction in PIP induced by the SGC activator, sodium nitroprusside (SNP, 1.05 mg kg- 1, i.v.). SNP significantly (P <0.05) reduced by 65% the bronchoconstriction induced by nerve stimulation at 10 Hz. Methylene blue did not effect baseline PIP in sham-stimulated controls. The airway effects of methylene blue and SNP were not associated with their cardiovascular effects. 6. a-Chymotrypsin (2 units kg-', i.v.) significantly potentiated vagally-induced bronchoconstriction by a further 63% at 2.5 Hz, by a further 95.6% at 5 Hz but did not potentiate the increase in PIP at 10 Hz. alpha-Chymotrypsin also potentiated (by 116%) capsaicin-induced bronchoconstriction. Vasoactive intestinal peptide (VIP, 10 ig kg-' i.v. infused over min) significantly reduced by 70% the increase in PIP induced by NKA (0.1 .Lmol kg-' i.v., infused over 30 s). 7. The combination of a-chymotrypsin (2 units kg-', i.v.) and L-NAME (5 mg kg-', i.v.) significantly potentiated NANC bronchoconstriction by a further 304% at 2.5 Hz, an increase in PIP which was greater than that induced by either a-chymotrypsin or L-NAME alone (P <0.05). 8. We conclude that endogenous NO and a bronchodilator peptide, possibly VIP, released in association with nerve stimulation, as well as activation of soluble guanylyl cyclase, regulate the magnitude of NANC neurogenic bronchoconstriction in guinea-pigs in vivo.
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PMID:Regulation of NANC neural bronchoconstriction in vivo in the guinea-pig: involvement of nitric oxide, vasoactive intestinal peptide and soluble guanylyl cyclase. 767 32

1. The mediators of non-adrenergic non-cholinergic (NANC) relaxation of the longitudinal muscle of rat proximal, middle and distal colon were examined in vitro. 2. Electrical transmural stimulation (TMS) of proximal, middle and distal segments of rat colon induced NANC relaxations which were inhibited by tetrodotoxin (1 microM), but not by atropine (1 microM) or guanethidine (4 microM). 3. In the proximal colon, L-nitro-arginine (N5-nitroamidino-L-2,5-diaminopentanoic acid) inhibited the TMS-induced NANC relaxation and L-arginine (1 mM) reversed this inhibition. Nitric oxide (0.3-10 microM) induced relaxation of the proximal segment. 4. NANC relaxation of the proximal segments was still evident after desensitization to vasoactive intestinal peptide (VIP). A VIP antagonist (VIP 10-28, 10 microM) had no effect on the TMS-induced NANC relaxation, which was also resistant to alpha-chymotrypsin (2 units ml-1) and a substance P antagonist ([D-Pro2, D-Trp7,9]substance P, 1 microM). 5. In the middle colon, L-nitro-arginine did not inhibit the TMS-induced NANC relaxation in 6 of 9 preparations tested and partially inhibited the relaxation in the other 3 preparations. L-Arginine did not reverse the partial inhibition. 6. Complete desensitization to VIP was not achieved in the middle colon. The VIP antagonist had no effect on the TMS-induced NANC relaxation. After alpha-chymotrypsin treatment of the segment, desensitization of the segments to substance P, or in the presence of the substance P antagonist, the TMS-induced NANC relaxation was augmented. 7. In the distal colon, L-nitro-arginine did not have any significant effect on the TMS-induced relaxation and nitric oxide did not induce relaxation. The VIP antagonist significantly inhibited TMS-induced NANC relaxation. Alpa-Chymotrypsin-treatment of the distal segments resulted in significant inhibition of NANC relaxation. No desensitization to substance P was achieved. Treatment with the substance P antagonist had no effect. 8. These results suggest that nitric oxide is the mediator of the NANC inhibitory response in the proximal region of rat colon; in the middle colon, substance P acts as an excitatory neurotransmitter, antagonizing the NANC relaxation caused by the mediator of the response, which is still uncertain. Our results suggest that that VIP is the most likely candidate as a NANC transmitter in the distal colon.
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PMID:Mediators of nonadrenergic, noncholinergic inhibition in the proximal, middle and distal regions of rat colon. 768 May 92