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)

We investigated whether exposure of guinea pig tracheal tissue to hypochlorous acid (HOCl) or hydrogen peroxide (H2O2) by perfusion through the airway lumen affected the responsiveness of airway muscle to ACh, KCl, or substance P in the presence or absence of 1 microM phosphoramidon, an inhibitor of neutral endopeptidase (NEP). Pairs of tracheal segments were immersed in a Krebs solution (pH 7.40 at 37 degrees C) and connected to perfusion circuits so that the lumen of one segment of each pair could be perfused with Krebs solution while the other was perfused for the same time (10 min) with either 0.1 microM HOCl or 10 mM H2O2. Segments after perfusion were cut into rings of similar size and placed in muscle chambers so that airway muscle force generation in vitro could be measured on stimulation by cumulative agonist doses. In addition, cell homogenates were made from other, similarly perfused tracheal segments to assess NEP activity using reverse-phase, high-pressure liquid chromatography (HPLC). We found that smooth muscle of mucosa-intact guinea pig airways perfused with HOCl, but not H2O2, was hyperresponsive to substance P but not to ACh or KCl. HOCl-perfused rings were not different from Krebs solution-exposed rings pretreated with phosphoramidon. There was no increase in substance P responsiveness of HOCl-exposed airways in which the mucosa had been removed before testing in vitro. The substance P hyperresponsiveness of HOCl-exposed, mucosa-intact airways was associated with decreased NEP activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HOCl causes airway substance P hyperresponsiveness and neutral endopeptidase hypoactivity. 169 6

1. We have studied the effect of substance P (SP) on catecholamine (CA) secretion evoked by prolonged field stimulation from the perfused rat adrenal gland in vitro. 2. Previous studies show that SP has an inhibitory effect on the nicotinic response in a number of different tissue preparations. In the present study, we found that SP at concentrations from 10(-7) to 10(-6) M markedly increased CA secretion evoked by prolonged high-frequency field stimulation but not that evoked by low-frequency field stimulation. 3. In the absence of field stimulation SP by itself had no direct effect on CA secretion. This indicates that SP acts as a neuromodulator rather than a neurotransmitter to increase CA secretion from the adrenal medulla. 4. The nicotinic receptors were still functional following a period of prolonged field stimulation (120 min) because CA secretion was markedly increased in response to the nicotinic agonist dimethylphenylpiperazinium (DMPP). 5. Capsaicin pre-treatment reduced CA secretion evoked by prolonged field stimulation and the facilitatory action of SP on CA secretion lasted longer in these capsaicin-pre-treated rats than in controls, indicating that SP-containing capsaicin-sensitive fibres innervating the adrenal medulla may be involved in the regulation of CA secretion. 6. In parallel with the increase in CA secretion, 3H overflow from the splanchnic nerve pre-labelled with [3H]choline was also increased by SP. The increase in CA secretion by SP lasted longer than the increase in 3H overflow. These results suggest that SP facilitates CA secretion from the adrenal gland at two levels: (1) pre-synaptically by facilitating ACh release from splanchnic nerve terminals, and (2) post-synaptically by modulating the nicotinic secretory response by protection against nicotinic desensitization of secretion. 7. The present studies provide further evidence that endogenous SP in the splanchnic nerve may modulate CA secretion during stress.
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PMID:Substance P increases catecholamine secretion from perfused rat adrenal glands evoked by prolonged field stimulation. 169 77

Release of [3H]acetylcholine ([3H]ACh) was examined in a submucous plexus preparation obtained from the guinea pig small intestine in vitro. Constant-current field stimulation evoked ACh output; this output was dependent on the stimulus frequency applied. Maximal release was observed at 10 Hz; this release was blocked by tetrodotoxin (1 x 10(-6) M) or in Ca2(+)-free buffer. Serotonin [5-hydroxytryptamine (5-HT)] stimulated the release of ACh dose dependently, with an ED50 of 5 x 10(-7) M. Substance P was ineffective, while vasoactive intestinal peptide weakly stimulated ACh secretion. Several neuropeptides were tested on their ability to modulate 5-HT-evoked ACh release. Dynorphin A inhibited 5-HT-stimulated ACh release, while Met-enkephalin was without any effect. Both somatostatin and galanin were effective modulators, with an inhibitory effect in the submicromolar range and an excitatory effect at higher concentrations. The response characteristics of the cholinergic neurons of submucosal plexus differ markedly from those of the myenteric plexus. These distinct features form an important framework for future functional studies on submucous plexus neurons.
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PMID:Modulation of submucosal cholinergic neurons by 5-hydroxytryptamine and neuropeptides. 170 72

The interaction between bombesin and acetylcholine acting on smooth muscle of the stomach wall was investigated in two species of teleost fish. Oncorhynchus mykiss (rainbow trout) and Gadus morhua (Atlantic cod). Acetylcholine or bombesin alone has an excitatory effect on the stomach muscle. The effect on contraction amplitude of acetylcholine (10(-6)-10(-5) M) alone is about 10-times greater than the effect of bombesin (10(-9)-10(-7) M). In molar terms however, bombesin is more potent than acetylcholine. Bombesin (10(-8)-10(-7) M) added 0.5-3 min prior to acetylcholine potentiates the effect of acetylcholine in a dose-dependent manner. The potentiation is most pronounced in circular muscle preparations, but is present also in longitudinal muscle preparations. Bombesin affects the response to carbachol (10(-6) M) with a similar potentiation, indicating that the potentiation is not caused by inhibition of choline esterase activity. Atropine (10(-6)-10(-5) M) abolishes the response to bombesin plus acetylcholine as well as the response to acetylcholine alone. Tetrodotoxin (10(-6) M) does not block the effect of acetylcholine, bombesin or the combination acetylcholine plus bombesin. Substance P (10(-9)-10(-7) M) which has a similar excitatory effect on the stomach muscle as bombesin, does not potentiate the effect of acetylcholine. Immunohistochemistry has shown the presence of strong bombesin-like immunoreactivity in stomach nerves of the cod and weak bombesin-like immunoreactivity in rainbow trout nerves. In addition, bombesin-like immunoreactivity was demonstrated in endocrine cells in the gastric and intestinal mucosa of both species. It is concluded that bombesin, contained either in nerve fibres or in mucosal endocrine cells, specifically potentiates the effect of acetylcholine in the fish stomach.
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PMID:Bombesin potentiates the effect of acetylcholine on isolated strips of fish stomach. 170 14

Microiontophoresis of acetylcholine onto cheek pouch arterioles of the pentobarbital-anesthetized hamster results in both a local response at the pipette tip and a conducted dilator response. The conducted response is not dependent on blood flow, and its magnitude decays with distance from the site of stimulation. In an attempt to define the mechanism responsible for activation of arteriolar conduction, vasoactive agonists directed toward different vascular wall cell types, receptor types, and second messengers were applied to arterioles by pressure-pulse microejection. As expected, microapplication caused a consistent arteriolar response at the site of application with each of the agonists tested (local response). However, a high degree of variability was observed among agonists in their ability to produce conducted responses. Acetylcholine, muscarine, and phenylephrine, invariably induced both local and conducted responses. In contrast, bradykinin, substance P, papaverine, isoproterenol, and adenosine, though consistently inducing local responses, displayed a highly variable ability to induce the conducted responses. When conduction was observed, the arteriolar response was similar regardless of the agonist used to induce the response. Microejection of sodium nitroprusside or arginine vasopressin produced local arteriolar responses with no evidence of a conducted response regardless of the dose. These studies reveal previously undetected heterogeneity among microvessel responses and may reflect variations in the coupling mechanisms linking the local vasomotor response to the conducted response.
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PMID:Heterogeneity in conducted arteriolar vasomotor response is agonist dependent. 170 43

1. Endothelium-dependency of vasodilator responses was compared in helical strips of monkey cerebral and superficial temporal arteries contracted with prostaglandin F2 alpha. Acetylcholine produced an endothelium-dependent relaxation in the temporal arteries, but did not consistently alter the tone of cerebral arteries. 2. Adenosine 5'-triphosphate (ATP) produced a transient contraction followed by a relaxation in the temporal and cerebral arteries; removal of the endothelium partially attenuated the relaxation of the cerebral arteries and markedly suppressed the relaxation in the temporal arteries. The dependency of adenosine 5'-diphosphate (ADP)-induced relaxations on the endothelium was also greater in temporal arteries than in cerebral arteries. 3. Histamine-induced relaxations in the temporal arteries were independent of the endothelium and were reversed to contractions by cimetidine. Cerebral arterial relaxations induced by histamine were partly dependent on the endothelium. Relaxations caused by substance P were reversed to contractions by removal of the endothelium in the temporal arteries, whereas the peptide did not consistently alter the tone of cerebral arteries. 4. The Ca2+ ionophore, A23187, relaxed the temporal and cerebral arteries to a similar extent; removal of the endothelium abolished these relaxations. Glyceryl trinitrate elicited similar relaxation of cerebral and temporal arteries, and these were independent of the endothelium. 5. These findings clearly indicate heterogeneity in the endothelium-dependency of several vasodilator responses in monkey intra- and extracranial arteries, although the ability of these arteries to respond to A23187 and glyceryl trinitrate does not appear to differ. The heterogeneous responses observed so far could therefore be due to different distributions of receptors or to variation in receptor-effector coupling in endothelial cells.
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PMID:Comparison of endothelium-dependent responses of monkey cerebral and temporal arteries. 171 6

1. The isolated hepatic artery of the rabbit contracted to exogenously applied noradrenaline (NA). There was no significant difference in the maximal contraction or the EC50 value in vessels where the endothelium was present and in endothelium-denuded preparations. 2. Acetylcholine (ACh) induced a vasodilatation of vessels preconstricted with NA which was entirely dependent on the endothelium. 3. Adenosine 5'-triphosphate (ATP), 2-methylthio ATP, adenosine and sodium nitroprusside induced concentration-dependent, sustained relaxations of vessels in which tone had been induced with NA. The relaxation responses were not reduced after removal of the endothelium. 8-Phenyltheophylline antagonized the relaxation response produced by adenosine, but not that due to ATP at lower concentrations. The maximum response to ATP was reduced in the presence of 8-phenyltheophylline. 4. alpha,beta-Methylene ATP produced further contraction of vessels preconstricted with NA in both endothelium-denuded preparations and in vessels where the endothelium remained intact. 5. Immunohistochemical analysis was used to show the presence of nerve fibres containing substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) in the hepatic artery. Application of SP induced a concentration-dependent relaxation which was entirely dependent on the presence of an intact endothelium. CGRP and VIP, however, elicited concentration-dependent relaxations which were independent of the endothelium. 7. It is concluded that in the rabbit hepatic artery, responses to ACh are dependent on the presence of intact endothelium. P1-, P2x- and P2y-purinoceptors, mediating relaxation to adenosine, vasoconstriction to ATP and vasodilatation to ATP respectively, are located on vascular smooth muscle. Furthermore, CGRP and VIP mediate a direct vasodilatation of smooth muscle both in the absence and the presence of the endothelium, whereas SP produces a relaxation via receptors located on the endothelium.
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PMID:Endothelium-dependent and endothelium-independent vasodilatation of the hepatic artery of the rabbit. 171 28

Previous studies have demonstrated that focal electrical stimulation of regions within the brainstem of a decerebrate bird will elicit all the normal patterns of avian locomotion. However, electrical stimulation can activate a variety of neuronal elements within the radius of effective current spread, including axons of passage traversing the stimulation point. To restrict activation to neuronal cell bodies within the immediate vicinity, we have utilized direct intracerebral injection of neurotransmitters, their agonists and antagonists, into identified brainstem locomotor regions. To undertake these studies, birds (geese or ducks) were placed in a stereotaxic frame and decerebrated under halothane anesthesia. After completion of surgery, several discrete locomotor regions were first identified with electrical microstimulation. Acetylcholine (ACh) and excitatory amino acid (EAA) agonists and antagonists, as well as Substance P were then slowly infused into each brainstem region. Any change in locomotor behavior was recorded by electromyographic techniques. When injected into a variety of sites, carbachol (an ACh nicotinic (AChN) and muscarinic (AChM) agonist) and pilocarpine (an AChM agonist) evoked locomotion, whereas atropine (an AChM antagonist) blocked locomotion. N-methyl-D-aspartate NMDA), but not glutamate, also elicited locomotion or reduced the current intensity threshold for electrically-evoked locomotion. The NMDA-induced locomotion evoked locomotion. The NMDA-induced locomotion could be blocked by the injection of glutamic acid diethyl ester (GDEE, an EAA antagonist) or D-2-amino-5-phosphonopentanoic acid (AP5) into the same site. Finally. Substance P also evoked locomotion. The above observations strongly suggest that brainstem electrically-stimulated locomotion in decerebrate birds is not due to activation of fibers traversing a brainstem locomotor region, but instead, is due to the activation of receptors located on neuronal cell bodies, dendrites or presynaptic terminals in the immediate vicinity of the micropipette tip. After correlating our findings with similar lamprey and mammalian studies, the comparable discoveries serve to underscore the suggestion that the neuroanatomical substrates underlying the brainstem control of locomotion appear to be highly conserved in all vertebrates.
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PMID:Avian locomotion activated by brainstem infusion of neurotransmitter agonists and antagonists. I. Acetylcholine excitatory amino acids and substance P. 171 6

A method of quantitatively measuring tachykinin-induced salivation in conscious, male, Sprague-Dawley rats is described. Salivation is quantified by determining the weight of a preweighed, absorbant foam cube after it has been used to swab the oral cavity of a tachykinin challenged rat. Salivation is induced by intravenous (i.v.) injection of sialogogues (microgram/kg) via the lateral tail vein. Measurements are made immediately after injection. Substance P (Sub.P), Sar9, Met (O2) 11Substance P (Sar9 Sub.P), a selective neurokinin (NK) 1 receptor agonist, Physalaemin and Eledoisin are equipotent sialogogues as determined by this method. Neurokinin A (NKA), the endogenous NK2 receptor agonist, is 0.27 (0.14-0.46) times as potent as Sub. P, while (Suc-[Asp6, MePhe8]Substance P(6-11), (senktide), a selective NK3 receptor agonist, only induced salivation at 300 microgram/kg. Acetylcholine (Ach) is only 0.006 (0.002-0.012) times as potent as Sub.P. Treatment with the neurokinin antagonist [D-Arg1, D-Trp7,9 Leu11]-Substance P (spantide) dose-dependently inhibits Sub. P stimulated salivation. Atropine dose-dependently inhibits Ach induced salivation but is inactive against Sub.P-induced salivation. These data are consistent with literature values and indicate that this method provides a simple, quantitative model, free of any possible anesthetic side effects, for the measurement of neurokinin stimulated salivation and the assessment of potential neurokinin antagonists in vivo.
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PMID:Measurement of tachykinin-induced salivation in conscious rats. 171 93

1. Ciliary beat frequency in epithelial outgrowths from cultured explants of Rana pipiens palate changed markedly from second to second. 2. Acetylcholine (10(-8) to 10(-3) M) and substance P (1.35 x 10(-7) to 1.35 x 10(-5) M) increased and stabilized ciliary beat frequency. The effect of acetylcholine and part of the effect of substance P were blocked by atropine (10(-4) M). 3. Acetylcholine appears to act directly and substance P both directly and indirectly through the release of acetylcholine.
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PMID:Stimulation of frog ciliated cells in culture by acetylcholine and substance P. 172 38


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