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)

1. Rapid change of bath temperature from 37 degrees C to 27 degrees C and vice versa caused longitudinal contraction of the isolated guinea-pig ileum. 2. Tetrodotoxin, tropicamide, noradrenaline, isoprenaline, morphine, and the met-enkephalin analogue FK 33-824 depressed the responses or accelerated the fade of the contraction induced by rapid cooling when added after the response had reached its maximum. 3. Hexamethonium had no influence on the responses. 4. Physostigmine potentiated all responses and reversed the fade of contraction induced by rapid cooling when added after this contraction had reached its maximum. 5. The effects of rapid cooling or warming were not altered in preparations made tachyphylactic to substance P; the response to rapid warming, but not cooling, was partially inhibited under tachyphylaxis to 5-hydroxytryptamine. 6. Antazoline, phentolamine, naloxone, and indomethacin did not block the responses. 7. Capsaicin firt potentiated and subsequently depressed the responses to both rapid cooling and warming. 8. The results indicate that rapid change of bath temperature induces longitudinal contraction by excitation of postganglionic cholinergic fibres.
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PMID:Longitudinal contraction of isolated guinea-pig ileum induced by rapid cooling. 9 5

Since the original observations by Von Euler and Gaddum, considerable interest has developed regarding the role of substance P in smooth muscle function. The purpose of the present investigation was to evaluate the effect of intravenously administered substance P on the vivo motor function of the lower esophageal sphincter (LES). Intraesophageal pressures were monitored by an assembly of polyvinyl catheters attached to pressure transducers and a recorder. The catheters were continuously perfused with bubble-free water. Administration of 5, 10, 25, 50, and 100 ng per kg of substance P stimulated the LES, respectively, 16, 32, 57, 147, and 169% above control values. Tetrodotoxin, phentolamine, hexamethonium, methysergide, and bilateral cervical vagotomy did not alter the response of the LES to substance P. Atropine in 40-, 250-, and 500-microgram per kg doses significantly but partially inhibited the response of the LES to substance P. It is concluded that subtance P is a potent stimulant of the LES. The stimulatory effect of substance P may involve both cholinergic muscarinic and noncholinergic mechanisms. It is conceivable that substance P may be a modulator of LES pressure, although the exact physiological significance is not clear at the present time.
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PMID:Effect of substance P on the lower esophageal sphincter of the opossum. 66 13

Tachykinin receptors mediating substance P-induced secretion were examined in muscle-stripped segments of guinea-pig ileum set up in flux chambers. Changes in the short-circuit current (Isc) served as an index of active, electrogenic ion transport. Substance P evoked a transient increase in Isc which was concentration-dependent. The maximal change in Isc occurred at 1 microM concentration. [Sar9,Met(O2)11]-substance P, a neurokinin 1 (NK-1) receptor agonist, evoked a similar concentration-dependent increase in Isc. [Nle10]NKA(4-10) (1 microM) or [Pro7]NKB (1 microM), selective NK2 and NK3 agonists, respectively, had minimal effects on Isc. CP-96,345 (5 microM), a nonpeptide NK-1 antagonist, and the peptide NK-1 antagonist, GR82334 (1 microM), reduced the secretory response to substance P (50 nM) in the presence and absence of tetrodotoxin (0.2 microM). The NK2 antagonist, [Tyr5,D-Trp6,8,9,Arg10]NKA(4-10) MEN 10207 had no effect on the substance P response. Tetrodotoxin (0.2 microM) significantly reduced, but did not abolish the Isc response to substance P (1 microM) and [Sar9,Met(O2)11]substance P (1 microM). The substance P response was unaltered by 5 microM atropine and 50 microM mecamylamine. Piroxicam (10 microM) or pyrilamine (10 microM) or a combination of both had no effect on the tetrodotoxin-resistant substance P response. Electrical field stimulation evoked a biphasic increase in Isc which was significantly reduced by 0.2 microM tetrodotoxin. Atropine (5 microM) reduced the first peak of the biphasic response and mecamylamine (50 microM) had no effect. Similarly, 5 microM CP-96,345 and 1 microM GR82334 did not alter the EFS-induced change Isc. The results suggest that substance P-evoked secretory responses are independent of histamine or prostaglandins. Substance P responses are mediated by an NK-1 receptor type on enteric neurons and possibly epithelial cells.
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PMID:Neurokinin 1 receptors mediate substance P-induced changes in ion transport in guinea-pig ileum. 127 53

Determination of guinea pig ileal response to electrical field stimulation (EFS) before and after complete adrenergic and cholinergic blockade showed that the nonadrenergic noncholinergic excitatory (NANC-e) response contributed 40% to the total contractile response. NANC-e responses were reproducible to consecutive identical EFS. Tetrodotoxin significantly blocked the NANC-e response. The NANC-e responses obtained before and after treatment of the tissues with receptor antagonists of histamine (pyrilamine), substance P ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP) and serotonin (5-HT1 & 5-HT2) indicated that the response could be blocked by substance P and serotonin antagonists. Only the serotonin antagonist cyproheptadine produced a dose-dependent blockade. Both substance P and serotonin are suggested to play an important role in the NANC-e neurotransmission.
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PMID:Blockade of electrical field stimulation-induced nonadrenergic noncholinergic (NANC) excitatory response of the guinea pig ileum. 128 71

The release of substance P-like immunoreactive material (SPLI) from the vascularly perfused stomach of the rainbow trout, Oncorhynchus mykiss, was studied. In most cases, SPLI was detected in the collected vascular perfusate during experimental resting conditions. Distensions of the stomach, accomplished by a water-filled intragastric balloon, produced an initial rapid relaxation of the stomach, followed by a slow further relaxation and a stimulation of contractile activity. The amount of SPLI in the vascular perfusate was significantly elevated during the distension period. Tetrodotoxin had no effect on the response to distension or on the release of SPLI during distension, indicating release from tetrodotoxin-insensitive neurons or endocrine cells. The results suggest that a substance P-like peptide may be involved in the contractile response and/or in the maintenance of muscular tone during gastric distensions in the rainbow trout. Infusion of capsaicin had no effect on the release of SPLI. However, capsaicin caused an increase in vascular flow, an effect that could be repeated on a second infusion of capsaicin, indicating that the action may not be specific to sensory neurons.
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PMID:Release of substance P-like immunoreactive material from the stomach of the rainbow trout. 137 9

Substance P (SP) caused a concentration-dependent increase in short-circuit current of rat isolated colonic mucosal preparations (ED50 10 nM). The SP antagonist [D-Arg1,D-Pro2,D-Trp7,9, Leu11]SP (50 microM) did not increase short-circuit current. Tetrodotoxin (3.1 microM) reduced the effect of a maximum concentration of SP (300 nM). This reduction was increased when tetrodotoxin was given with [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP. Increases in short-circuit current produced by electrical field stimulation were not reduced by [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP. It is concluded that SP is not a transmitter at the neuroepithelial junction in rat colonic mucosa.
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PMID:Evidence against substance P as a neurotransmitter at the neuroepithelial junction in rat colonic mucosa. 138 May 51

1. Neurokinin A (NKA) is a mammalian tachykinin distributed principally in the nervous system, including the myenteric innervation of the gut. 2. NKA may be involved in neurogenic inflammation and as a modulatory factor in the diarrhoea associated with mucosal inflammation of inflammatory bowel disease (ulcerative colitis). 3. We evaluated the effect of NKA on the short-circuit current ISC, assumed to reflect electrogenic chloride secretion, across muscle-stripped rat colonic mucosa mounted in Ussing chambers. 4. Serosal addition of NKA produced a concentration-dependent (0.1-100 nM) increase in ISC with an EC50 (half-maximal effective concentration) value of 7.5 nM. The maximum (mean +/- S.E.M.) increase in ISC (microA/cm2) for NKA was 111 +/- 10. 5. Tetrodotoxin (0.5 microM) and bumetanide (10 microM), but not atropine (1.0 microM), hexamethonium (100 microM) or pyrilamine (10 microM), significantly inhibited NKA-induced increases in ISC. 6. The response to NKA was attenuated by 45 min pre-treatment with antisera raised against vasoactive intestinal polypeptide (VIP). Moreover, prior desensitization to VIP attenuated the effect of NKA. 7. These studies suggest that NKA increases ISC in rat colon, in part, through a non-cholinergic neural mechanism involving VIP.
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PMID:Neurokinin A increases short-circuit current across rat colonic mucosa: a role for vasoactive intestinal polypeptide. 165 54

The effects of substance P and related tachykinins on short-circuit current were determined in submucosa-mucosa sheets of guinea pig distal colon. Substance P, neurokinin A, eledoisin and physalaemin evoked a concentration-dependent increase in short-circuit current with a rank order of potencies of substance P = physalaemin greater than eledoisin = neurokinin A. The substance P response was reduced in chloride-free solutions or after addition of furosemide. Tetrodotoxin, atropine, mecamylamine and pyrilamine reduced the response to substance P. The substance P antagonist, [D-Arg1,D-Phe5,Trp7,9,Leu11]-substance P, reduced the response to neural stimulation and to exogenous substance P. The results suggest that substance P evokes anion secretion by activating cholinergic and noncholinergic neurons and by releasing histamine.
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PMID:Tachykinin-induced anion secretion in guinea pig distal colon: role of neural and inflammatory mediators. 168 41

In the guinea pig isolated perfused lung, we have examined the relationship between the effects of capsaicin and neuropeptide release and the possible existence of an axon reflex arrangement. Bolus injections into the pulmonary artery of capsaicin (1-100 pmol), substance P (10-1,000 pmol), and neurokinin (NK) A (10-100 pmol) produced a concentration-dependent bronchoconstriction, whereas calcitonin gene-related peptide (CGRP, 20-40 nmol) was without effect. Repeated administration of capsaicin at 40- to 60-min intervals was not associated with tachyphylaxis. These data support the presence of a NK2- (or NKA) type of tachykinin receptor in the guinea pig airways. Tetrodotoxin (0.3-3 microM) inhibited the effect of capsaicin, indicating that an axon reflex was operant. Capsaicin increased overflow of CGRP-like immunoreactivity (-LI) and NKA-LI, the latter only during concurrent infusion of the enkephalinase inhibitor phosphoramidon (3 microM). Phosphoramidon also increased overflow of CGRP-LI, suggesting that both NKA and CGRP were catabolized by a similar enzyme. The purine nucleoside adenosine did not cause any detectable overflow of CGRP-LI, indicating that neuropeptides may not be involved in adenosine-evoked bronchoconstriction and that bronchoconstriction per se does not induce neuropeptide overflow. Capsaicin and NKA had only minor effects on buffer flow, whereas substance P produced pulmonary vasoconstriction. These data clearly demonstrate that capsaicin acts via an axon reflex in the guinea pig airways. Supramaximal concentrations of capsaicin are needed to detect neuropeptide overflow, but the possibility exists that released neuropeptides mediate its effects.
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PMID:Capsaicin-induced bronchoconstriction and neuropeptide release in guinea pig perfused lungs. 169 65

The hypothesis that substance P (SP) elicits both direct and indirect responses on the canine proximal colon was tested using two different in vitro preparations. The mucosa contained the muscularis mucosa and the attendant submucosal plexuses whereas the epithelium, being devoid of both, was functionally "nerve-free." Dose-dependent stimulation was noted on both preparations, increases in peak current (microamperes per squared centimeter) as well as charge transfers (millicoulombs per squared centimeter) were monitored. Tetrodotoxin significantly reduced mucosal responses whereas atropine and the H1 antagonists mepyramine and diphenhydramine had only marginal effects. None of these agents affected the responses of the epithelium to SP. Indomethacin significantly reduced responses in both preparations. Removal of Na+ or Cl- or the use of C- channel blockers (9-anthracene carboxylic acid and N-phenylanthranilic acid) produced a significant reduction of SP responses across the epithelium. Thus, SP has both direct and indirect affects on the colon; activation of the cyclooxygenase pathway could be significant.
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PMID:Epithelial and mucosal preparations from canine colon: responses to substance P. 169 22


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