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)

Cultured bovine endothelial cells were seeded onto the intimal surface of endothelium-denuded rings of canine coronary artery. These rings did not previously relax to acetylcholine, substance P, bradykinin, and A23187. After seeding, the same rings relaxed to bradykinin and A23187, but not to acetycholine or substance P. Indomethacin pretreatment did not affect these responses. Cells from the same source were then grown to confluence on microcarrier beads, poured into small columns, and perfused with Krebs' solution. The perfusate from the columns was bioassayed on endothelium-denuded rings of coronary artery from either the dog or pig. Challenge of the column in the presence of indomethacin with either bradykinin or A23187 as well as acetylcholine or substance P caused release of a substance that relaxed both types of artery. Its activity half-life was 6.4 +/- 0.4 sec at 37 degrees C and it was hydrophilic and negatively charged. Prostacyclin (PGI2) as a candidate for EDRF was ruled out because 1) indomethacin failed to block its release and 2) the pig coronary artery, although insensitive to PGI2, relaxed to the endothelium-derived substance. These results show that, in response to a number of dilator drugs, cultured endothelial cells release a vascular relaxing substance (EDRF) that has characteristics similar to the EDRF of normal endothelium. The chemical nature of EDRF awaits clarification.
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PMID:Release and properties of endothelium-derived relaxing factor (EDRF) from endothelial cells in culture. 388 74

The effect of bladder filling on vesical blood flow was studied in anesthetized cats. The pelvic nerves were sectioned and the bladder venous outflow was recorded by a drop counter. Filling of the bladder induced a sustained increase in vesical blood flow, related to the bladder volume. Thus, injection of 10, 20 and 30 ml. of saline decreased bladder vascular resistance by 27, 47 and 52 per cent, respectively. This vasodilation occurred despite a steady state increase in bladder pressure by 25 to 50 cm. H2O. Upon emptying of the bladder, blood flow decreased towards control values. The response was unaffected by alpha-adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol) and muscarinic cholinoceptor blockade (atropine). The vasodilation was eliminated by papaverine, indicating that the response was not due to a rearrangement of the vessels at large bladder volumes. The vasodilation was not associated with any increase in the concentrations of vasoactive intestinal polypeptide (VIP) or substance P in the venous effluent blood. Indomethacin significantly reduced the vasodilatation induced by filling. We conclude that local mechanisms, possibly involving release of prostaglandins, are involved in the vasodilation following bladder distension.
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PMID:Changes in vascular resistance in the feline urinary bladder in response to bladder filling. 405 65

Rabbit bladder body was stimulated to contract by a number of agonists, of which bradykinin was the most potent, and ATP one of the least potent substances tested. The atropine-resistant component of the neurogenic response was unaffected by 2 X 10(-5) M chlorpheniramine or 10(-6) M methysergide, doses which suppressed responses to histamine or 5HT. Indomethacin 10(-5) M, or 10(-5) M capsaicin both reduced the atropine-resistant component. Following treatment with 10(-6) M atropine and 10(-5) M prazosin, 10(-4) M ANAPP3 produced a further suppression of the response, but did not antagonize the response to ATP. In the bladder body, the transmitter(s) responsible for the neurogenic response may be acetylcholine and prostaglandins and possibly ATP and substance P.
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PMID:A study of the atropine-resistant component of the neurogenic response of the rabbit urinary bladder. 614 2

The influence of substance P (SP) and somatostatin (SS) on contractions induced by electrical field stimulation, ATP and carbachol were investigated in isolated rabbit urinary bladder. Some experiments were also carried out in rat and guinea-pig detrusor. When added cumulatively to rabbit and rat preparations, SP and SS caused a gradual increase in tone of the preparations. There were no effects on the electrically induced contractions. In rabbit and rat detrusor pretreated with guanethidine, atropine and indomethacin, the contractile response to nerve stimulation was markedly reduced. In this situation SP and SS caused 2-4 fold increase in the electrically induced contractions. Indomethacin abolished the tonic response to ATP in the rabbit detrusor, and reduced the initial phasic contraction by about 30%. Both SP and SS were able to restore the phasic contraction to the level obtained before indomethacin addition. The contractions induced by carbachol in rabbit and rat detrusor were not affected by SP and SS, not even in indomethacin pretreated preparations. The SP-antagonist (D-Pro2, D-Phe, D-Trp9)-SP was tested in isolated rabbit, rat, and guinea-pig detrusor. Concentrations of the antagonist which effectively inhibited contractions induced by a submaximum concentration of SP had no effect on the contractile response to electrical field stimulation in rabbit and guinea-pig preparations, and rather tended to increase the contractions in the rat detrusor. The results suggest that neither SS nor SP is the mediator of excitatory non-cholinergic, non-adrenergic activation of rabbit urinary bladder. A role as local modulators of neuromuscular transmission cannot be excluded.
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PMID:Substance P and somatostatin and excitatory neurotransmission in rabbit urinary bladder. 617 Dec 17

In isolated detrusor from guinea-pigs and rats substance P (SP) induced concentration-dependent phasic contractions. Rabbit detrusor strips responded to SP with an initial phasic and an ensuing tonic contraction. The concentration-response curve to SP in this preparation had a biphasic appearance. Eledoisin (E) caused contractile responses similar to those of SP when tested on the guinea-pig detrusor. Somatostatin was tested on the rabbit urinary bladder; it caused a concentration-dependent rise in basal tone, but no phasic contraction. The responses to SP and E were not affected by tetrodotoxin or physostigmine. They were only partly inhibited by high concentrations of atropine and the anticholinergic drug PR 197. Noradrenaline and isoprenaline caused a concentration-dependent inhibition of the peptide induced responses in guinea-pig bladder; at high concentrations in the amines this inhibition was almost complete. Indomethacin did not affect the SP induced contractions in the guinea-pig bladder, reduced the responses in the rabbit detrusor, but increased them in the rat bladder. Contractions elicited by SP and E were rapidly diminished or abolished after 30 min. treatment in a calcium-free medium. The responses were also inhibited by the calcium antagonist nifedipine. In guinea-pig preparations depolarized by potassium (127 mM) both SP and E caused a contractile response approximately 20% of that obtained in normal Tyrode solution. It is concluded that SP and E cause contraction of detrusor by a direct effect on the smooth muscle cells, and that this response is dependent on the extracellular calcium concentration. Prostaglandins may be involved in the SP-induced response of the rabbit detrusor.
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PMID:Contractile effects of some polypeptides on the isolated urinary bladder of guinea-pig, rabbit, and rat. 617 55

Peptide and non-peptide agents were tested for their stimulatory or inhibitory effects on circular strips of guinea pig isolated tracheae. Substance P, eledoisin, physalaemin, neurotensin, angiotensin, histamine and carbachol were found to contract, while noradrenaline, dopamine, bradykinin, nucleotides (AMP, ADP, ATP) and prostaglandins (PGE1, PGE2, PGA2) induced concentration-dependent relaxations of tracheae contracted with substance P or carbachol. Indomethacin (2.8 X 10(-6) M) significantly potentiated the effect of substance P and blocked that of bradykinin. The contractions to substance P of tissues treated with indomethacin were not modified by atropine, methysergide, diphenhydramine, cimetidine, propranolol, phentolamine, [Leu8]-ATII, [Leu8]-des-Arg9-bradykinin, naloxone and baclofen. The order of potency of C-terminal fragments of substance P was: hexa(6-11) greater than hepta(5-11) greater than substance P greater than = octa(4-11). It is concluded that the guinea pig isolated trachea is a pharmacological preparation sensitive to numerous agents and useful for studying structure-activity relationship and the mechanism of cellular action of several peptides, particularly substance P.
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PMID:Pharmacological effects of peptides on tracheal smooth muscle. 618 32

1. The role of substance P (SP) in adrenergic transmission has been studied in the isolated perfused rat mesentery. 2. Intra-arterial perfusion of SP (4 x 10(-9) to 4 x 10(-7)M) produced a dose dependent potentiation of norepinephrine (NE) induced vasoconstrictor responses and a shift of the log dose--response curve to the left. 3. Saralasin, a specific antagonist of angiotensin II (ang. II) when perfused at a concentration of 3 x 10(-9)M did not change the NE responses as such. However, the potentiating effect of SP could not be demonstrated in the presence of saralasin. 4. Indomethacin, a prostaglandin (PG) synthetase inhibitor, when perfused at a concentration of 2.8 x 10(-6)M, markedly attenuated the vascular responses to NE, which could not be normalized by the addition of SP. 5. It appears that SP's potentiating effect on NE responses in the perfused rat mesentery simulates ang. II and not prostaglandins. A direct non-specific post synaptic sensitizing effect of SP on vascular smooth muscle cell, for its potentiating property, cannot be ruled out.
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PMID:Modulatory effects of substance P on norepinephrine induced vasoconstrictor responses in the rat mesentery. 618 72

Two substance P (SP) analogues, [D-Pro2, D-Phe7, D-Trp9]-SP (DPDPDT) and [D-Trp7,9]-SP (DT79), previously described as tachykinin antagonists, have been shown to contract the rat colon muscularis mucosae preparation. The maximum response exhibited by these analogues was about 30% that of the SP maximum, suggesting that they were acting as partial agonists relative to SP. The responses to DPDPDT were unaffected by pretreatment with mepyramine, methysergide or [Sar1, Ile5, Ala8]-angiotensin II, which abolished the responses to histamine, 5-hydroxytryptamine (5-HT) and angiotensin II, respectively. Methysergide also did not affect the responses to DT79; the other antagonists were not tested against this analogue. Indomethacin and cimetidine also had no inhibitory effect. Atropine (2 microM) was present in all experiments to prevent indirect muscarinic effects. Phenoxybenzamine did not affect the dose-response curves to SP, eledoisin-related peptide (ERP), kassinin, eledoisin or physalaemin, nor did it affect the responses to individual doses of DPDPDT or DT79. However, in the absence of atropine, it shifted the carbachol dose-response curve markedly to the right, and reduced its maximum. The tachykinin antagonist [D-Pro4, D-Trp7,9,10]-SP4-11 reduced the responses to individual matched doses of DPDPDT, DT79 and SP to the same degree, whilst leaving responses to 5-HT or angiotensin II unaffected. This suggested that DPDPDT and DT79 were acting at the same receptor as SP. The inhibitory effects of DPDPDT on responses to SP, ERP and kassinin, and that of DT79 on responses to SP, were analysed. All four combinations yielded data compatible with an interaction at only one receptor, although DPDPDT appeared slightly more potent at inhibiting responses to kassinin. The results are discussed in the light of the proposed existence of multiple tachykinin receptor subtypes. The possible influence of differential metabolism of tachykinin analogues is also considered.
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PMID:A study of [D-Pro2, D-Phe7, D-Trp9]-substance P and [D-Trp7,9]-substance P as tachykinin partial agonists in the rat colon. 620 95

The modulatory effect of bradykinin on excitatory nonadrenergic noncholinergic (e-NANC) neural constrictor responses was examined in anesthetized guinea pig airways in vivo. e-NANC responses were obtained by bilateral vagal stimulation in the presence of atropine (1 mg/kg i.v.) and propranolol (1 mg/kg i.v.). Indomethacin (5 mg/kg i.v.) and captopril (1 mg/kg i.v.) were pretreated to avoid the indirect effects of bradykinin by producing prostaglandins and to prevent endogenous breakdown of bradykinin, respectively. Bradykinin (0.01-1 nmol/kg i.v.) potentiated e-NANC responses in a dose-dependent manner. The potentiation was significant with 0.1 and 1 nmol/kg of bradykinin, 22.7 +/- 3.2% (mean +/- S.E.; P < .01) and 34.5 +/- 4.7% (P < .01), respectively), compared with that in sham-injected control animals (-4.7 +/- 3.6%). The potentiation of e-NANC responses by bradykinin (1 nmol/kg i.v.) was abolished by the subsequent administration of a bradykinin B2 receptor antagonist, HOE140 (0.1 mumol/kg i.v.), that was without effect on e-NANC responses by itself. The contraction induced by exogenous administration of substance P (1 nmol/kg i.v.) was not affected by the same dose of i.v. bradykinin; the change in substance P-induced bronchoconstriction was 9.2 +/- 8.3% with and 3.2 +/- 3.6% without bradykinin (P > .05). These results suggest that bradykinin potentiates e-NANC responses in guinea pig airways in vivo via B2 receptors which are possibly on prejunctional sites.
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PMID:Modulation of nonadrenergic noncholinergic neural bronchoconstriction by bradykinin in anesthetized guinea pigs in vivo. 750 96

Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2 agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.
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PMID:Contractile effects of bradykinin on the isolated human small bronchus. 750 45


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