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)

Dihydropyridine (DHP) calcium channel antagonists, which inhibit the slowly inactivating or L-type cardiac calcium (Ca) current, have been shown to be ineffective in blocking 45Ca influx and Ca-dependent secretion in a number of neuronal preparations. In the studies reported here, however, the antagonist DHP nifedipine inhibited both the L-type Ca current and potassium-evoked substance P (SP) release from embryonic chick dorsal root ganglion (DRG) neurons. These results suggest that, in DRG neurons, Ca entry through L-type channels is critical to the control of secretion. The inhibition of Ca current by nifedipine was both voltage and time-dependent, significant effects being observed only on currents evoked from relatively positive holding potentials maintained for several seconds. As expected from these results, nifedipine failed to inhibit L-type Ca current underlying the brief plateau phase of the action potential generated from the cell's normal resting potential; likewise, no significant effect of the drug was observed on action potential-stimulated SP release evoked by electrical field stimulation. The results of this work are discussed in terms of an assessment of the role of L-type Ca channels in neurosecretion.
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PMID:Dihydropyridine inhibition of neuronal calcium current and substance P release. 244 5

Calcium plays a central role in modulating many physiologic events. We have investigated the role of calcium channel blockade in the control of basal (n = 6)- and substance P-stimulated (n = 6) intestinal transport in the isolated perfused rabbit ileum. Twenty-centimeter segments of ileum, harvested from New Zealand rabbits, were arterially perfused at 1.5 ml/min with an oxygenated modified Krebs buffer solution containing washed human red cells (Hct = 15-20%) and 2.5 mM Ca2+. The intestinal lumen was perfused at 2 ml/min with an isotonic solution containing 1.2 mM Ca2+ and [14C]PEG as a nonabsorbable volume marker. The infusion of verapamil (1 microgram/min) significantly reduced (P less than 0.05) the basal secretion of H2O, and Cl-. Verapamil prevented the secretory effect of substance P infused at 0.25 microgram/min. Intraarterial verapamil had no effect on vascular perfusion pressure. These data indicate that calcium channel blockade has significant effects on basal- and substance P-stimulated intestinal secretion and suggest that transmembrane calcium fluxes function as major determinants of basal- and secretagogue-stimulated intestinal transport.
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PMID:The effect of calcium channel blockade on basal- and substance P-induced intestinal secretion. 245 37

The effect of extracellular calcium on the release of calcitonin gene-related peptide (CGRP) induced by electrical field stimulation from enteric nerves of isolated rat ileum was studied; the effect of high potassium, veratridine and caffeine was also examined. Release of endogenous substance P from enteric nerves was also measured for comparison. Electrical field stimulation (10 Hz, 0.3 ms for 2 min) of the ileum preparation caused a significant (P less than 0.001) increase in the release of CGRP and substance P from enteric nerves. The evoked, but not the basal, release of both CGRP and substance P was inhibited in the presence of tetrodotoxin (TTX). The release of CGRP and substance P induced by electrical stimulation was abolished in Ca2+-free medium containing CDTA and also in normal medium containing the calcium channel blocker cadmium chloride (CdCl2), with no change in the level of the basal release of both peptides. However, potassium depolarization (76 and 110 mM) failed to evoke an increase in the release of endogenous CGRP, although it did cause an increase in the release can be induced by mobilization of calcium from intracellular Ca2+ stores. Veratridine, on the other hand, did not cause an increase in CGRP release, although substance P and VIP release was induced by veratridine from the same preparations. The results of the present study have demonstrated that CGRP release from enteric nerves requires the presence of extracellular calcium but, unlike substance P and most other transmitters reported to show calcium-dependent release, potassium depolarization does not induce CGRP release from enteric nerves of rat ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of calcitonin gene-related peptide from rat enteric nerves is Ca2+-dependent but is not induced by K+ depolarization. 246 7

Endothelin-1 (ET-1), a 21 amino acid peptide, has recently been identified and shown to produce a potent and prolonged constriction of mammalian blood vessels in vitro. We have studied the effect of local infusion of this peptide on resistance vessels in the hindlimb of the anesthetized greyhound dog. Incremental doses of ET-1 (3-200 pmol/min) were infused into the left femoral artery. Doses above 10 pmol/min produced a slowly progressive reduction in hindlimb blood flow in a dose dependent fashion, maximally reducing flow by 79.5% +/- 3.2 from 152.3 +/- 29.1 ml/min to 27.8 +/- 5.8 ml/min (+/- SEM, p less than 0.015), with a concomitant rise in vascular resistance. In the control vessel (right femoral artery) there were no statistically significant changes in blood flow observed. Onset time of the response to ET-1 was 3 min, whereas spontaneous recovery of the flow occurred at 30 min following cessation of the infusion. We demonstrated transient reversal of constriction in this arterial model during coinfusion with endothelin-1 (100 pmol/min) of dihydropyridine calcium channel blocking agent nicardipine (0.5-20 nmol/min), substance P (0.5-50 fmol/min), adenosine (10-10,000 pmol/min), and isosorbide dinitrate (0.001-0.1 mg/min).
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PMID:Endothelin-1 is a potent long-lasting vasoconstrictor in dog peripheral vasculature in vivo. 247 15

The effects of vasoactive intestinal peptide (VIP) and substance P (SP) on the amount of proenkephalin A (ProEnk A) mRNA in cultures of bovine adrenal chromaffin cells were examined. Exposure of chromaffin cells to 5 microM VIP for 24 h produced a significant elevation in ProEnk A mRNA. The stimulatory effect of VIP could be abolished by the presence of the calcium channel blocker D600 or actinomycin D but was not affected by the nicotinic antagonist hexamethonium. The results suggest that VIP may induce transcription of ProEnk A mRNA by a Ca2+-dependent, non-cholinergic mechanism. By contrast, SP (5 microM) had no effect on the amount of ProEnk A mRNA. Since VIP is found in nerve terminals and the ganglion cells within the adrenal medulla, this peptide could be an endogenous regulator of adrenal enkephalin gene expression.
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PMID:Vasoactive intestinal peptide stimulates proenkephalin A mRNA expression in bovine adrenal chromaffin cells. 247 28

Substance P-like immunoreactivity was assayed in superfusates of guinea-pig ureters following stimulation of afferent fibres with capsaicin, potassium chloride and the calcium channel agonist Bay K 8644. Capsaicin-evoked release of substance P-like immunoreactivity was calcium-dependent but unaffected by cobalt. Under appropriate conditions release was dose-related (ED50 = 610 nM) and reproducible. Selective desensitization to capsaicin could be demonstrated following prolonged exposure to different doses of capsaicin. No desensitization to capsaicin was observed following afferent fibre stimulation with a combination of Bay K 8644 and K+, which released a similar amount of substance P-like immunoreactivity as a desensitizing capsaicin stimulus. These data suggest that depletion of releasable substance P-like reactivity is unlikely to account for selective desensitization of ureteric primary afferent fibres to capsaicin.
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PMID:Desensitization and capsaicin-induced release of substance P-like immunoreactivity from guinea-pig ureter in vitro. 247 71

Ruthenium red has recently been found to inhibit the effects of capsaicin on peripheral terminals of sensory neurones. Thus the effects of ruthenium red on the responses of the guinea-pig isolated ileum to capsaicin, acetylcholine (ACh), substance P (SP) and nicotine were investigated. Ruthenium red, 5 mumol/l, abolished responses to capsaicin 1.5 mumol/l and nicotine 2 mumol/l, and shifted the concentration-response lines to ACh and SP to the right. Pretreatment of ileum preparations with ruthenium red, 12.5 mumol/l for 2 min, prevented desensitization of ileum responses to capsaicin tested 30 min later. Tetrodotoxin, 1 mumol/l, abolished the response to capsaicin on control preparations and those pretreated with atropine, 5 mumol/l, ruthenium red, 12.5 mumol/l or spantide, 10 mumol/l. It is proposed that capsaicin acts via a specific receptor coupled to a receptor-operated membrane calcium channel, and that ruthenium red binds irreversibly to the calcium channel part of the complex but reversibly to some other site which prevents the action or binding of capsaicin at its specific receptor.
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PMID:The effects of ruthenium red on the response of guinea-pig ileum to capsaicin. 247 75

High-affinity binding sites for endothelin have been found in a human placenta membrane preparation. 125I-endothelin bound to placenta membranes at 20 degrees C with an association half-time of 30 min, whereas the binding was only slowly reversed with a dissociation half-time of 250 min. In saturation experiments, a single class of high-affinity binding sites was identified with an apparent dissociation constant (KD) of 24 pM and a maximal density of 240 fmol per mg of protein. The binding of 125I-endothelin was half-maximally inhibited by cold endothelin at a concentration (IC50) of 140 pM. In contrast, no inhibition was found at 10(-4) M for a variety of vasoactive peptides such as angiotensin II, vasopressin, neuropeptide Y, substance P, CGRP, bradykinin, leucine enkephalin or dynorphin A. Similarly, the binding was modulated neither by the calcium channel blockers nifedipine, verapamil or diltiazem, nor by the calcium channel agonist Bay k 8644. There was also no effect with the structurally-related bee venom apamin. Using this membrane preparation, endothelin-like activity could be measured in the medium of cultured human endothelial cells by competition binding technique.
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PMID:Specific receptors for endothelin on membranes from human placenta. Characterization and use in a binding assay. 254 8

We investigated the effect of a neuropeptide, substance P, on the electrical and ion transport properties of dog trachea. Posterior mucosal tissues were mounted in Ussing chambers and bathed with Krebs-Henseleit solution, pH 7.4, at 37 degrees C. The solution was gassed with 95% O2, 5% CO2. Substance P (10(-7)M) added to the mucosal bath elicited within seconds a rapid rise in short circuit current with a peak response of 23 microA.cm-2 and an increase in tissue conductance of 0.63 mS.cm-2 (p less than 0.001, n = 20). In 6 experiments, 36Cl and 22Na fluxes were measured under short circuit conditions and they revealed that net Cl secretion increased from 1.46 +/- 0.41 to 2.30 +/- 0.74 mueq.cm-2 X h-1 (mean +/- SE, p less than 0.05). This increase was brought about by enhancement of unidirectional submucosa to lumen flux. Net Na absorption of 0.63 +/- 0.09 did not change significantly (0.49 +/- 0.16). Short circuit current response to substance P was not modified by prior tissue incubation with atropine, phenoxybenzamine, propranolol, or naloxone. Removal of mucosal bath calcium and the presence of calcium channel blocker verapamil did not abolish tissue response to substance P. These findings suggest that nerve fibers containing substance P may play a role in regulation of ion transport across the trachea. This action does not appear to be related to the cholinergic, adrenergic, or oplate receptors.
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PMID:Substance P stimulation of chloride secretion by canine tracheal mucosa. 257 65

(+/-) Tiropramide hydrochloride, its D and L optical isomers and some of its metabolites were characterized in a number of in vitro pharmacological tests. Tiropramide showed broad spectrum antispasmodic activities on the isolated stomach of guinea pig electrically stimulated; on the longitudinal muscles of the ileum of guinea pig stimulated by electrical impulses, BaCl2, acetylcholine, histamine, serotonin, substance P and cholecystokinin octapeptide (CCK-8); on the spontaneous contractions and on the electrical inhibition of the jejunum of rabbit; on the spontaneous contractions and on the contractions provoked by BaCl2 and acetylcholine of the ascending colon of the rat; on the contractions provoked by BaCl2, acetylcholine, histamine and cerulein of the circular muscles of the gall bladder of the guinea pig; on the spontaneous contractions of the pyel-ureter preparation of the guinea pig; on the contractions of the uterus of the rat provoked by oxitocin, serotonin, acetylcholine, PGF2; on the spontaneous contraction of the portal vein of the rat; on the constriction of the tail artery of the rat provoked by electrical stimulation, epinephrine and ergotamine; on the contractions of the aortic strip of the rabbit stimulated by norepinephrine; on the contractions of the strip of bovine coronary artery depolarized by HCl. In general tiropramide had antispasmodic effect at 5-60 mumol/l concentration. It was more potent than papaverine on contractions provoked by electrical or chemical stimuli, and was less potent or ineffective on spontaneous and "physiological" contractions of the different smooth muscle preparations. Tiropramide had small effects on vascular smooth muscles and showed very small calcium channel blocking activity.
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PMID:Pharmacological characterisation of the smooth muscle antispasmodic agent tiropramide. 259 Feb 61


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