Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Nicotine produced a transient contraction of rabbit isolated iris sphincter muscle, a parasympathetic ganglion-free tissue. The response to nicotine was antagonized by hexamethonium, but was insensitive to tetrodotoxin (TTX). While single treatments with atropine, capsaicin or [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP) partially blocked the response, combined treatment abolished it. 2. Chronic treatment of animals with nicotine added to the drinking water (about 12 mg kg-1 per day) had no effect on the responsiveness to nicotine or the pharmacological properties of nicotine-induced contraction. 3. These results suggest that acetylcholine and tachykinin(s) released via sodium channel-independent mechanisms from nerve terminals of parasympathetic and primary sensory nerves, respectively, are involved in the nicotine-induced contractile response.
 ...
PMID:Mechanism of action of nicotine in isolated iris sphincter preparations of rabbit. 322 72

The possible role of peptides locally released from sensory nerves in the control of cardiac contractility and the coronary vascular tone was investigated in the present study. Immunohistochemical investigations revealed that calcitonin gene-related peptide (CGRP) -like immunoreactivity (-LI) was colocalized in sensory ganglia and in nerve fibres in the heart with substance P (SP) -LI. CGRP-LI was associated with myocardial cells, blood vessels and epicardia and endocardia in the atria while in the ventricles, CGRP-LI was mainly seen close to blood vessels and very few fibres were present in the myocardium. The level of CGRP-LI was three to four times higher in the right atria than in the ventricles. The tissue content of CGRP-LI was markedly reduced by systemic pretreatment with capsaicin, suggesting a sensory origin. Activation of capsaicin-sensitive cardiac C-fibres by K+, nicotine, bradykinin, ouabain and ischaemia was associated with a release of CGRP as indicated by an increased overflow from the isolated perfused guinea-pig heart. In addition, K+ and capsaicin induced the release of neurokinin A. Nicotine and K+ evoked the release of neuropeptide Y, which is present in sympathetic nerves. CGRP induced a prolongation of the action potential plateau phase in atrial myocytes, increased the velocity of relaxation and evoked positive chronotropic and inotropic effects. Capsaicin induced electrophysiological and contractile effects similar to those of CGRP. Furthermore, specific high affinity binding sites for CGRP were demonstrated in the rat heart and in the atrium CGRP stimulated adenylate cyclase activity. The capsaicin effects were abolished after systemic capsaicin pretreatment, which did not influence the stimulatory effects of CGRP or noradrenaline (NA), however. Repeated administration of CGRP to the same atrial preparation induced tachyphylaxis. After CGRP tachyphylaxis the stimulatory effects of capsaicin but not of NA were absent. The stimulatory actions of capsaicin on atrial contractility therefore seem to be evoked by CGRP. The inhibitory effects of capsaicin on ventricular contractility were not dependent on mediators released from capsaicin-sensitive sensory nerves. CGRP, SP and capsaicin induced coronary vasodilatation in the pig in vivo and in vitro. The vasodilatory effect of SP was subject to rapid tachyphylaxis and endothelium-dependent. Neither the CGRP- nor the capsaicin-induced relaxation was influenced by SP tachyphylaxis or removal of the endothelium. It is therefore suggested that CGRP is a more likely candidate than SP as a causative agent in the vasodilatory response seen upon activation of cardiac sensory nerves.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Calcitonin gene-related peptide and tachykinins in relation to local sensory control of cardiac contractility and coronary vascular tone. 326 56

1. Strips of longitudinal muscle can be obtained from guinea-pig ileum either retaining or free from Auerbach's plexus.2. The denervated strip is unresponsive to electrical stimulation by brief shocks, whether given singly or in trains; it also fails to respond to nicotine or dimethylphenylpiperazinium iodide (DMPP), and eserine causes no spasm.3. Denervated strips neither contain detectable acetylcholine (< 0.4 ng/mg), nor release it spontaneously (< 5 pg/mg/min) or in response to stimulation (< 31 pg/mg/min). The acetylcholine metabolism of the innervated strip is therefore that of the adherent Auerbach's plexus. Innervated strips had a mean acetylcholine content of 28 ng/mg, a mean resting output of 94 pg/mg/min and an output in response to stimulation at 10 c/s of 700-1200 pg/mg/min.4. By comparing the responses of innervated and denervated strips it was concluded that arecoline, methylfurmethide, alpha,beta-ethylal-gamma-tri-methylammonium propanediol iodide (2268 F), muscarine, histamine, tremorine, oxytocin, and substance P, like acetylcholine, act primarily on the smooth muscle directly; and that angiotensin, barium, potassium, m-bromophenyl choline ether and 5-hydroxytryptamine have a progressively increasing proportionate effect on the nerve plexus. Nicotine and DMPP were inactive in the absence of the plexus.5. The longitudinal muscle with its accompanying plexus contains about one quarter of the acetylcholine of the whole ileum, and is responsible for about one fifth of the output to electrical stimulation.6. The volley output of acetylcholine by the innervated strip declines sharply as rate of stimulation increases. Output of acetylcholine was reduced by morphine and by cocaine, particularly when resting or when stimulated at low rates.7. Acetylcholine output by whole ileum from guinea-pig declines in the absence of glucose, but is insulin-independent. Output by strips of ileum from rats made diabetic with alloxan was similar to that from normal rats.8. The similarity in properties of acetylcholine output from innervated strips, where it must come from nervous tissue, to that from whole ileum, and the insulin-independence of output from whole ileum suggest that the whole of the acetylcholine output of intestine is nervous in origin.9. Comparison of the acetylcholine metabolism of the innervated strip with that of the superior cervical ganglion suggests that the typical features of the former (high resting output, high volley output at low rates, low minute output at high rates of stimulation, and sensitivity to morphine) may be linked with the absence of specialized neuro-effector junctions and represent a relatively primitive transmission process.
 ...
PMID:The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. 429 53

Substance P, a peptide endogenous to the splanchnic nerve, is known to inhibit the acetylcholine-and nicotine-induced release of catecholamines from isolated adrenal chromaffin cells. In the present study the effect of substance P on desensitization of catecholamine release from these cells was examined. Substance P (10(-5) M) completely protected against desensitization of catecholamine release produced by acetylcholine at 37 degrees C or 23 degrees C and by nicotine at 23 degrees C; substance P also afforded appreciable protection against nicotine-induced desensitization at 37 degrees C. The peptide had no effect on K+-induced desensitization of catecholamine release. Like substance P, d-tubocurarine also prevented nicotinic desensitization. Substance P prevented both of two components of nicotinic desensitization, i.e. the Ca2+-dependent component and the Ca2+-independent, depletion-independent component of desensitization. Substance P had little effect on subsequent catecholamine uptake, indicating that substance P's protection against desensitization is a result of facilitation of catecholamine release rather than inhibition of catecholamine reuptake. Nicotine-induced catecholamine release and nicotinic desensitization of catecholamine release were Na+-independent, although substance P's inhibition of nicotine-induced catecholamine release was reduced by extracellular Na+. These in vitro studies suggest a similar role for substance P in vivo: substance P's protection against nicotinic desensitization may ensure a maintained output of adrenal catecholamines during stress, when the splanchnic nerve releases large amounts of acetylcholine.
 ...
PMID:Substance P protects against desensitization of the nicotinic response in isolated adrenal chromaffin cells. 619 67

1. The neuronal release of acetylcholine (ACh) and its autoregulation by neuromodulators, substance P (SP) and methionine enkephalin (MEK), have been studied using superfused rodent cerebral slices. Nicotine exerts significant effects on autoregulation of ACh release, which may have toxicological implications. 2. Positive and negative feedback systems have been postulated for autoregulation of ACh release. The components of the positive feedback system include a muscarinic (Ms) receptor, SP, and activation of Ca2+ influx. Low levels of ACh in the biophase of the cholinergic synaptic gap may trigger the positive feedback system, and high levels of ACh may trigger the negative feedback system. 3. There are also neuronal pathways for direct reciprocal regulations of SP and MEK. 4. Low concentrations of nicotine triggers the release of ACh followed by MEK and SP. Release of SP causes neurogenic inflammation. 5. Nicotine and its metabolite, cotinine, activate platelet activating factor (PAF)-hydrolase and thereby enhance the turnover rate of PAF. This effect may contribute to tobacco-induced arterial thrombosis in peripheral and central nervous systems.
 ...
PMID:Neuropharmacology of nicotine: effects on the autoregulation of acetylcholine release by substance P and methionine enkephalin in rodent cerebral slices and toxicological implications. 754 60

Because sensory neuropeptides improve survival of critical skin and muscle flaps in rats, skin nociceptive sensory nerve function in blister healing was examined. Sensory nerve ablation by unilateral hindlimb denervation or cutaneous axon reflex enhancement by 14 days systemic nicotine treatment (5 mg kg-1 day-1) decreased and increased, respectively, peripheral motor functions of nociceptive (peptidergic) skin nerves. Effects on nociception were measured by a radiant heat tail-flick test. Axon reflex flares were evoked by transdermal iontophoresis of acetylcholine or noxious electrical stimulation under pentobarbitone 40 mg kg-1 anaesthesia. Resultant changes in cutaneous microvascular blood flux were measured non-invasively by laser Doppler flowmetry. In nicotine-treated rats compared with placebo-treated controls, acetylcholine-evoked axon reflex flare was enhanced by 240% (p < 0.01) without enhancement of electrically evoked flare. Thus, nicotine-sensitized nociceptors show stimulus specificity in their enhancement of neurogenic flare responses. No significant changes were seen in other endothelial-dependent or smooth muscle-dependent microvascular dilator responses. Nicotine-treated rats had prolonged tail-flick withdrawal latencies to noxious radiant heat stimuli compared with placebo-treated controls (p < 0.05), suggesting an antinociceptive or analgesic effect of nicotine-treatment. Neurogenic effects on wound healing rate were assessed by measuring the dimensions of standardized blisters twice daily. The blisters were raised on hindpaw glabrous skin using a constant weight and diameter of compressed dry ice pellet applied for 30 secs at constant force. Dry-ice blisters raised on the hindpaw 14 days post-denervation were significantly slower to heal completely (42 days) than controls (30 days: P < 0.05) and the surrounding inflammation was reduced. By contrast, nicotine-treated rats showed more rapid blister healing (25 days) than controls (30 days), seen only in the later phase after day 15. Finally, resting substance P release from blisters, after direct cutaneous nerve stimulation, appears to be enhanced in nicotine-treated rats. Thus nociceptive innervation appears critical for inflammation and rapid healing of blisters in rat skin. The data signal a possible important role for neuropeptides in these processes and question the function of nicotinic receptors on sensory nerves.
 ...
PMID:The role of skin nociceptive afferent nerves in blister healing. 771 28

We characterized plasma exudation induced by direct inhalation of cigarette smoke in anesthetized, artificially ventilated guinea pigs, using Evans blue dye as a plasma marker, and investigated the neurogenic mechanisms underlying the response. Cigarette smoke increased plasma exudation in the lower trachea, main bronchi, and proximal intrapulmonary airways in a dose-related manner. Exudation was rapid in onset and was maintained for 0.5 to 2 h, depending upon airway level. Exudation was not reduced after removal of the particular phase of the smoke, nor by atropine, phentolamine, propranolol, hexamethonium, antihistamines, or bilateral vagotomy. Nicotine, at a dose calculated to approximate that in the plasma of cigarette-exposed animals, did not increase airway plasma exudation. Cigarette smoke-induce exudation was blocked by capaicinization or by a substance P antagonist and was potentiated by phosphoramidon but not by captopril. Nedocromil sodium or morphine (0.1 mg/kg each intravenously) partially inhibited cigarette smoke-induced exudation but had no effect on the response to substance P. Inhibition by morphine, but not that by nedocromil sodium, was reversed by naloxone. Thus, direct inhalation of cigarette smoke induces a dose-related, long-lasting increase in airway plasma exudation that is due to vapor-phase activation of sensory-efferent nerves, release of sensory neuropeptides that mediate the exudative response via interaction with substance P receptors, and regulation by neutral endopeptidase. The inhibitory effect of nedocromil and morphine on cigarette smoke-induced airway plasma exudation occurs through inhibition of neurotransmission.
 ...
PMID:Mechanisms and modulation of airway plasma exudation after direct inhalation of cigarette smoke. 776 17

Nicotine (100 microM), but not electrical field stimulation or potassium chloride (0.1-3 microM), caused capsaicin (1 microM)- and tetrodotoxin (1 microM)-sensitive relaxations of guinea-pig isolated basilar artery precontracted with prostaglandin F2 alpha. Nicotine-induced responses were blocked by the neurokinin NK1 receptor antagonist, GR82334 (10 microM), but were unaffected by the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37) (1 microM). This suggests that nicotine activates capsaicin-sensitive sensory nerves in guinea-pig basilar artery to cause relaxation predominantly via substance P release. The vascular 5-HT1 receptor agonist, sumatriptan (0.3 and 3 microM), inhibited nicotine-induced relaxation (by 50 and 80% respectively); the inhibitory effect of sumatriptan (0.3 microM) was attenuated in the presence of the non-selective 5-HT1 receptor antagonist, methiothepin (0.1 microM). These data suggest that sumatriptan can inhibit sensory neurotransmission in guinea-pig basilar artery via activation of inhibitory prejunctional 5-HT1 receptors on sensory nerve terminals.
 ...
PMID:Activation of sensory nerves in guinea-pig isolated basilar artery by nicotine: evidence for inhibition of trigeminal sensory neurotransmission by sumatriptan. 795 91

Nitric oxide (NO) plays an important physiological role in regulating gastrointestinal motility. Involvement of endogenous NO was evaluated in the response to non-adrenergic, non-cholinergic (NANC) nerve stimulation of the dog sphincter muscle of Oddi. Transmural electrical stimulation (TES), nicotine (10(-5) M) and K+ (10 mM) produced only a relaxation in the sphincter muscle strips contracted with substance P, which was not potentiated by atropine. The TES-induced relaxation was abolished by tetrodotoxin (3 x 10(-7) M) and oxyhaemoglobin (1.6 x 10(-5) M), but not affected by atropine (10(-7) M), propranolol (10(-7) M), phentolamine (10(-7) M), indomethacin (10(-6) M), cholecystokinin (CCK, 10(-8) M) and vasoactive intestinal polypeptide (VIP, 10(-8) M). The relaxation was also abolished by treatment with NG-nitro-L-arginine (L-NA, 10(-5) M), an NO synthase inhibitor. Nicotine produced a transient relaxation, which was abolished by tetrodotoxin, hexamethonium (10(-5) M) and L-NA, but not affected by atropine and NG-nitro-D-arginine (D-NA, 10(-5) M). The addition of K+ elicited a transient relaxation, which was abolished by tetrodotoxin and L-NA. The inhibitory effects of L-NA were antagonized by L-arginine (10(-3) M). The presence of neurons containing nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was histochemically demonstrated in the sphincter of Oddi. These findings may indicate that TES, nicotine and K+ liberate NO from NANC inhibitory nerve which is involved in the relaxation of the dog sphincter of Oddi. The muscular tone does not seem to be regulated by cholinergic nerves under the experimental conditions used.
 ...
PMID:Functional role and histological demonstration of nitric-oxide-mediated inhibitory nerves in dog sphincter of Oddi. 857 10

1. The modulator effects of a series of neurotransmitters and related substances were tested on responses to adenosine 5'-triphosphate (ATP) at a recombinant P2x2 receptor expressed in defolliculated Xenopus oocytes. 2. Nicotine, 5'-hydroxytryptamine (5-HT), noradrenaline, adenosine, bradykinin and histamine (all 100 microM) potentiated the responses to ATP (3 microM). an effect found due to acidification of the bathing solution by these drugs. 3. Arachidonic acid, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP) (all 100 microM) and nerve growth factor (NGF; 50 ng ml-1) potentiated the responses to ATP (3 microM) through a largely or wholly pH-independent effect. 4. Small acidic and alkaline shifts, as little as 0.03 pH-units, enhanced or diminished the responses to ATP, respectively. A linear relationship existed between the degree of potentiation of the ATP-induced responses caused by nicotine, 5-HT, noradrenaline, adenosine, bradykinin and histamine and the potentiation of these responses induced by the addition of acid to the superfusate. 5. Since P2x receptors on sensory neurones include P2x2 subunits, the attendant acidosis and ATP-release associated with tissue injury may play a role in sensitizing sensory nerve fibres.
 ...
PMID:Potentiation of ATP-responses at a recombinant P2x2 receptor by neurotransmitters and related substances. 911 13


<< Previous 1 2 3 Next >>