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)

The effects of topical capsaicin on urinary bladder motility were investigated following saline-induced distension of the bladder wall in urethane-anaesthetized rats and compared to the effects of topical substance P and acetylcholine. Capsaicin and substance P produced similar excitatory effects in both quiescent and rhythmically contracting bladders, i.e., a TTX resistant tonic contraction followed by a series of rhythmic, TTX sensitive, phasic contractions. Acetylcholine, in doses equieffective in producing TTX resistant contractions was less effective than capsaicin or substance P in triggering neurogenic rhythmic contractions of bladder muscle. Atropine pretreatment prevented the neurogenic component of the excitatory effect of both capsaicin and substance P. Repeated applications of capsaicin but not of substance P led to desensitization. Bladders of animals pretreated (4 days before) with a large dose of s.c. capsaicin developed insensitivity to topical capsaicin and a larger volume of saline was required to trigger neurogenic rhythmic contractions of the detrusor muscle. These results suggest that capsaicin acts by interfering with the mechanism(s) regulating the threshold for the micturition reflex to occur.
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PMID:The effects of topical capsaicin on rat urinary bladder motility in vivo. 620 35

The inhibitory effect of atropine on phospholipid 32P labelling stimulated by muscarinic or alpha-adrenergic agonists was studied in isolated parotid cells. Atropine (10(-11) to 10(-4) M) had no effect on phospholipid 32P labelling in unstimulated cells. In contrast, 10(-8) to 10(-7) M atropine provoked a competitive inhibition of the cholinergic stimulation (i.e. this effect was completely wiped out at high agonist concentration). The atropine app. KD for the muscarinic receptor was 5 X 10(-9) M. Moreover, atropine inhibits the adrenergic stimulation of phospholipid 32P labelling by decreasing the efficacity and potency of the adrenergic agonists. The atropine app. KD for the alpha-adrenergic receptor can be estimated at 10(-5) M. This inhibition of alpha-adrenergic stimulation appears to be specific since atropine was without effect on the substance P or beta-adrenergic stimulation. At very low concentration (10(-10) - 10(-9) M) atropine seems to be a modulator (activator) of the muscarinic or adrenergic agonist-receptor complex. From the present data, it is suggested that atropine, besides its classical blocker effect at the muscarinic receptor, at high concentration is a specific alpha-adrenergic antagonist.
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PMID:Comparative effect of atropine on the adrenergic and muscarinic stimulation of phospholipid 32P labelling in isolated parotid cells: atropine, a possible blocker of alpha-adrenergic receptors. 632 Sep 38

The effects of three tachykinin NK1 receptor antagonists and a tachykinin NK2 receptor antagonist against substance P-induced contractions of the guinea-pig proximal colon longitudinal muscle were investigated. Atropine, tetrodotoxin and phosphoramidon did not affect the concentration-response curve for substance P (pEC50 = 7.8). The tachykinin NK1 receptor antagonist, 2S,3S-cis-CP 96345, competitively inhibited the contractions due to substance P (pA2 = 8.5; constrained pA2 = 8.9), but at higher concentrations (> or = 3 x 10(-7) M), 2S,3S-cis-CP 96345 also depressed the concentration-response curve for methacholine. The species-selective tachykinin NK1 receptor antagonists, WIN 51708 and WIN 62577 (both 1 x 10(-6) M), and the tachykinin NK2 receptor antagonist, SR 48968 (3 x 10(-7) M), had no effect. It is concluded that substance P induces contractions through the stimulation of tachykinin NK1 receptors on the smooth muscle cells. In this preparation, tachykinin NK2 receptors do not seem to be involved in the contractile action of substance P.
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PMID:Substance P-induced contractions of the guinea-pig proximal colon through stimulation of post-junctional tachykinin NK1 receptors. 750 52

N omega-Nitro-L-arginine methyl ester has been reported to have muscarinic receptor blocking activity whereas the nonesterified analog does not bind to muscarinic receptors. The present study was, therefore, undertaken to compare the inhibitory effects of N omega-nitro-L-arginine methyl ester with those of N omega-nitro-L-arginine on baseline tone and on vasodilator responses to acetylcholine, bradykinin, and substance P in the mesenteric vascular bed of the cat under constant flow conditions. Administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine in doses of 100 mg/kg i.v. increased baseline tone in the mesenteric vascular bed and inhibited mesenteric vasodilator responses to acetylcholine, bradykinin, and substance P. The increase in mesenteric arterial perfusion pressure and the decrease in vasodilator responses to the three endothelium-dependent vasodilator agents following administration of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine did not differ significantly. The nitric oxide synthase inhibitors did not attenuate vasodilator responses to agents that induce vasodilation by nonendothelium-dependent mechanisms and enhanced responses to the nitrovasodilators. Atropine blocked vasodilator responses to acetylcholine but did not alter responses to bradykinin or substance P. The similarity in the inhibitory effects of N omega-nitro-L-arginine methyl ester and N omega-nitro-L-arginine on responses to acetylcholine, bradykinin, and substance P suggest that the L-arginine analog, N omega-nitro-L-arginine, as well as the methyl ester of N omega-nitro-L-arginine, are useful probes for studying endothelium-dependent vasodilator responses in the mesenteric vascular bed of the cat.
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PMID:Comparative effects of N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, bradykinin, and substance P. 751 84

The aims of this study were (1) to define the effects of CCK-8s and related peptides on chicken ileum longitudinal smooth muscle and (2) to explore the mechanisms by which such effects occur. The effects of CCK-8s were assayed in vitro on chicken longitudinal ileal strips. CCK-8s produced contraction of ileal strips (EC50 8.8.10(-9) M). CCK-8ns and CCK-4 did not have remarkable contractile effects even when added at concentrations 200-times higher than the EC50 for CCK-8s. L365,260 slightly inhibited the effects of CCK-8s whereas L364,718 was ineffective. Tetrodotoxin (10(-6) M) markedly decreased the effects of CCK-8s. Atropine (10(-6) M) did not modify the neurally mediated effects of CCK-8s, whereas ketanserin (10(-5) M) decreased the response to CCK-8s. Substance P-desensitized preparations exhibited reduced responses to CCK-8s. Our results indicate that CCK receptors present in chicken ileum behave similarly but not identically to the CCK-A receptor described in mammals. Most of these CCK receptors are neurally located but a minor proportion is also present on smooth muscle. The neurally mediated response to CCK-8s does not involve cholinergic mechanisms, but serotonin and substance P releasing neurons.
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PMID:Mechanisms mediating the effects of cholecystokinin on avian small intestine longitudinal smooth muscle. 752 Jan 86

We studied effects of nicotinic, muscarinic, serotoninergic, dopaminergic, adrenergic, vasoactive intestinal peptide (VIP) antagonists, VIP, nitric oxide-synthase inhibitors and stimulators alone and in combination with tetrodotoxin on substance P (SP)-stimulated intraluminal tone of the isolated proximal, middle and distal rat colon. Tetrodotoxin significantly enhanced SP-stimulated intraluminal tonic pressure in the distal, but not in the middle and proximal colon. N omega-nitro-L-arginine methylester enhanced SP stimulation in all colonic segments, whereas L-arginine inhibited it partially and D-arginine did not affect it. Atropine and hexamethonium partially inhibited SP stimulation of the middle and distal colon. Tetrodotoxin completely abolished the effects of L-arginine, atropine and/or hexamethonium on SP stimulation. Propranolol, phentolamine, reserpine, telenzepine, naloxone, Mr 2266, a VIP antagonist (H9935) and ketanserin did not affect SP-induced colonic muscle stimulation. VIP strongly reduced SP-stimulated intraluminal pressure in all colonic segments. VIP(10-28), a putative VIP antagonist, produced similar inhibition of SP-stimulated intraluminal tonic pressure, but did not affect N omega-nitro-L-arginine methylester-induced enhancement of SP-stimulated intraluminal pressure in any segments. It is concluded that in the isolated rat colon SP-stimulated intraluminal pressure (mainly generated by circular muscles) by a direct action on colonic muscles over the whole colonic length and by simultaneous activation of neural cholinergic excitatory pathways in the middle and distal, of noncholinergic excitatory pathways in the proximal colonic segment, and by activation of nitric oxide-dependent inhibitory neural pathways. VIP seems not to be directly involved in this inhibitory pathway.
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PMID:Substance P activates rat colonic motility via excitatory and inhibitory neural pathways and direct action on muscles. 752 33

Pilocarpine releases histamine from mast cells of cat submandibular gland and rat liver. In the salivary gland, histamine is released into the saliva and venous outflow. Atropine blocks the salivation, but not histamine release from the submandibular gland into the blood. Histamine release from the gland could be due to a direct action of pilocarpine on tissue mast cells or to an indirect action of mediators (acetylcholine and peptides). These hypotheses were further investigated in our present studies on rat peritoneal mast cells. Our results show: (1) histamine release from rat peritoneal mast cells induced by pilocarpine (ED50 = 1.7 x 10(-2) mol/l) occurs at 1000-fold higher concentrations than by substance P (ED50 = 1.7 x 10(-5) mol/l) and in 6.5-fold higher concentrations than by atropine (ED50 = 2.6 x 10(-3) mol/l), (2) pilocarpine injected directly into the rat peritoneal cavity causes histamine release from peritoneal mast cells in 1.8-fold higher concentrations than from isolated rat peritoneal mast cells. These results would support the hypothesis that histamine release from cat submandibular gland is caused by peptidergic co-transmission during the stimulation of the organ.
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PMID:The mechanism of histamine release induced by pilocarpine from different tissues: studies on rat peritoneal mast cells. 752 51

Actions of substance P (SP, 10(-9) to 10(-6) M), neurokinin A (NKA, 10(-9) to 10(-6) M) and neurokinin B (NKB, 10(-10) to 10(-6) M) in the circular muscle of guinea pig ileum were investigated in segment and strip preparations, in which methacholine produced similar contractions. In the segment preparations, three tachykinins produced repeatedly occurring twitch-like contractions. Their efficacies were similar with the same maximal contractions, but their potencies were different (NKB > NKA = SP). Latency (38 sec) was observed before the initiation of contractions in response to NKA, but not to SP or NKB. Atropine (10(-6) M) and tetrodotoxin (3 x 10(-7) M) did not affect NKA-induced contractions, but inhibited SP- and NKB-induced contractions; the dose-response curves for SP and NKB were rightwardly shifted by atropine. The treatment with atropine brought out latency in the responses for NKB. In the strip preparations, SP did not substantially induce concentrations, but NKA and NKB produced twitch-like contractions after latent periods of 28 and 36 sec, respectively. The efficacy of NKA was similar to that in segment preparations, while that of NKB was much lower in strip preparations. Unlike in segment preparations, atropine did not inhibit contractions induced by the two tachykinins in strip preparations. These results suggest that tachykinins induce contractions through myogenic and neurogenic mechanisms, the latter of which may be inoperative in strip preparations.
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PMID:Tachykinin-induced contractions in the circular muscle of guinea pig ileum. 752 85

1. The local cardiac actions of substance P were examined in isolated perfused hearts and atria of the guinea-pig. 2. In both hearts and right atria, substance P caused negative inotropic and chronotropic effects. 3. Atropine (10(-6) M) or depletion of acetylcholine, by electrical stimulation and hemicholinium-3 perfusion, significantly attenuated the negative inotropic and chronotropic effects of substance P. alpha- and beta-adrenoceptor blockade by nadolol and phentolamine (10(-6) M each) did not prevent the negative inotropic and chronotropic effects of substance P. This indicates that cholinergic neurones, but not adrenergic neurones, partially mediate the effects of substance P. 4. There was no significant difference in the effects of substance P observed between groups with acetylcholine depletion and with cholinoceptor blockade. This suggests that substance P elicits its effects mainly through release of acetylcholine. 5. These results indicate that substance P has negative inotropic and chronotropic effects in guinea-pig hearts and right atria mediated partly by release of acetylcholine. Substance P also appears to have direct effects on cardiac tissue.
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PMID:Local cardiac effects of substance P: roles of acetylcholine and noradrenaline. 753 12

The effect of substance P on gastric motility was studied in conscious dogs by means of strain gauge force transducers chronically implanted on the gastric body, antrum, and a vagally-denervated fundic pouch. Intravenous infusion of substance P in the interdigestive state induced phasic contractions in the pouch and antrum. Atropine inhibited these contractions in the pouch and antrum. Hexamethonium enhanced substance P-induced contractions in the gastric antrum, but reduced those in the pouch. Pretreatment with phentolamine, propranolol, or naloxone did not affect substance P-induced contractions in the pouch and antrum. The intact gastric body scarcely reacted to substance P. Mean systemic blood pressure was lowered by substance P-infusion, but there was no dose-dependency in the reduction of the blood pressure, nor was it affected by the pretreatment with atropine or hexamethonium. These results suggest that 1) the vagal innervation influences the effect of substance P on motility in the gastric body, and that 2) substance P may stimulate postsynaptic excitatory cholinergic and presynaptic inhibitory neurons simultaneously in the gastric antrum.
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PMID:Effects of substance P on gastric motility differ depending on the sites and vagal innervation in conscious dogs. 753 62


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