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. 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.
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PMID:The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. 429 53

In helical strips of dog and monkey cerebral arteries contracted with prostaglandin F2 alpha, transmural stimulation and nicotine produced relaxations that were abolished by tetrodotoxin and hexamethonium, respectively. These responses were attenuated by quinidine, whereas relaxations of dog coronary arteries to transmural stimulation and isoproterenol were unaffected. Treatment with vasoactive intestinal polypeptide (VIP) and substance P (SP) abolished the relaxant response of cerebral arteries to repeated applications of VIP and SP, respectively; however, after VIP or SP, a normal relaxant response to transmural stimulation or nicotine was produced. Aminophylline suppressed relaxations induced by ATP but not by nerve stimulation. VIP, SP, and adenosine 5'-triphosphate (ATP) relaxed dog cerebral arteries; the responses were unaffected by quinidine. However, only VIP and ATP relaxed monkey cerebral arteries, and SP contracted the arteries. Acetylcholine contracted monkey arteries, in which transmural stimulation produced a relaxation. It may be concluded that nerves innervating the cerebrospinal wall are stimulated electrically and chemically by nicotine, resulting in the arterial relaxation. However, a vasodilator transmitter was not identified. Quinidine appears to selectively antagonize the action of the transmitters on cerebroarterial smooth muscle.
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PMID:Relaxant responses to transmural stimulation and nicotine of dog and monkey cerebral arteries. 612 21

Neurons located in the medial septum-nucleus of the diagonal band (vertical limb) area and antidromically activated by electrical stimulation of the fimbria were recorded in urethane anesthetized rats. Forty-five percent of these septo-hippocampal neurons (SHNs) discharged rhythmically in short bursts (mean burst frequency, 4 Hz). They were antidromically driven at short latencies from the fimbria. SHNs driven at long latencies (above 5 ms) were never bursting neurons. Fimbria stimulation also had a powerful inhibitory effect on the spontaneous activity of SHNs. The vast majority of the septo-hippocampal neurons were excited by the iontophoretic application of acetylcholine or cholinergic agonists, carbachol being the most effective. The acetylcholine-induced excitations were readily abolished by atropine. In contrast hexamethonium and mecamylamine were less effective. The rhythmic bursting activity could not be consistently altered by the iontophoretic application of cholinergic agonists or antagonists or of divalent cations. SHNs were also sensitive to various other putative neurotransmitters (substance P, GABA) known to play a role in the medial septal area. Bursting neurons and ACh-sensitive neurons were less frequent among unidentified medial septal neurons. The regulation of the septo-hippocampal cholinergic pathway is therefore not likely to be due to a direct feedback inhibition by locally released acetylcholine. However a strong inhibitory feedback could be exerted by the hippocampo-septal pathway impinging directly or indirectly on septo-hippocampal neurons.
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PMID:Septo-hippocampal and other medial septum-diagonal band neurons: electrophysiological and pharmacological properties. 614 26

1. The influence of substance P (SP) on spontaneous chemosensory discharge and on responses of the carotid chemoreceptors to various drugs has been investigated in pentobarbitone anaesthetized casts in which chemoreceptor activity was recorded from the peripheral end of a sectioned sinus nerve. 2. After an initial slight inhibition during the first 5--15 sec following the injection, SP (0.1--100 microgram I.A.) caused a dose-related increase in discharge which lasted for 45--300 sec in artificially ventilated cats, discharge being increased by about 50% on average. The increase was of shorter duration when the animals were allowed to breathe spontaneously. 3. The delayed increase in discharge was not secondary to the hypotension caused by SP, nor was it entirely due to changes in bronchomotor tone resulting from direct or indirect actions of SP, although such changes contributed to the response. It was not possible to determine whether the excitation was due to a direct effect of SP on the chemoreceptors. 4. Chemosensory excitation evoked by NaCN (5 microgram I.A.) was potentiated during I.A. infusions of SP and also 10--20 min after SP (10 microgram I.A.) had been injected. In contrast, responses to ACh (50 microgram I.A.) were inhibited. These effects may be due to a nicotinic-blocking action of SP on the carotid chemoreceptors. It was also found that the inhibitory action of dopamine (5 microgram I.A.) was reduced during SP infusion whereas that of 5-HT (10 microgram I.A.) was potentiated. 5. A sample of crude SP had effects on spontaneous chemoreceptor discharge and responses to NaCN and ACh which were qualitatively similar to those obtained using synthetic SP. 6. The physiological significance of the results is discussed and it is concluded that the interpretation depends upon whether or not SP is present in the cat's carotid body.
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PMID:Effects of substance P on carotid chemoreceptor activity in the cat. 615 9

It has been known for some time that NE and ACh can affect voltage-sensitive channels in the heart but it has only recently been appreciated that neurotransmitters (and certain peptides) can modulate voltage-sensitive channels in neurons. In addition to the effect on the action potential of embryonic chick sensory neurons described here, NE decreases the duration of spikes in rat superior cervical ganglion neurons (7). Serotonin prolongs action potentials recorded in Aplysia sensory neurons (9) and an as yet unidentified transmitter decreases an inward Ca++ current in the same cells (20). In the heart, one important consequence of the effect of NE and ACh on the action potential is a change in the strength and/or duration of contraction. In neurons, attention has been focused on the possibility that modulation of voltage-sensitive channels might result in a change in transmitter release. In Aplysia, the 5-HT induced prolongation of sensory neuron some spikes is associated with a dramatic augmentation of transmitter release at sensory nerve-motorneurone synapses (9) and the decrease in some inward Ca++ current is associated with presynaptic inhibition (20). Enkephalin, NE, GABA, and 5-HT can inhibit the evoked release of Substance P from cultured embryonic chick sensory neurons. These same drugs decrease ICa, apparently by decreasing the number of the conductance of voltage-sensitive Ca++ channels. The two phenomena may be related. It is significant in this regard that the same variability (between platings) in the ability of enkephalin to reduce Substance P release was also observed in the effect of enkephalin on action potential duration. Cells that released normal amounts of Substance P in the presence of enkephalin also exhibit spikes of normal duration in the presence of the peptide.
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PMID:Peptide and amine transmitter effect on embryonic chick sensory neurons in vitro. 616 32

Th effects on ganglion cell light responses and spontaneous activity of neurotransmitter candidates, applied by nebulizer spray and iontophoresis, were studied in the isolated carp retina. ACh, GABA, and substance P had strong effects on the ganglion cells; dopamine and the amino acids aspartate, glutamate, and glycine and only weak effects. ACh and substance P exerted their actions even when synaptic transmission was blocked by cobalt chloride, suggesting postsynaptic receptors for those agents on the ganglion cell membrane. The 3 amino acids and dopamine do not appear to act directly on the ganglion cells. The pharmacological sensitivity of ganglion cells was correlated with their physiological response type. About three-quarters of ON/OFF and half of other transiently responding ganglion cells were excited by micromolar concentrations of cholinergic agonists; most ON-center sustained ganglion cells were insensitive. The light response of some of the ACh-sensitive cells could be suppressed by cholinergic antagonists. Substance P generally excited ganglion cells with an ON-component in their light response. GABA inhibited cells of all response types, but affected least the OFF-center tonic cells. In view of these observations, and of corroborating histological evidence, we propose that ACh, GABA, and substance P are neurotransmitters that are released by amacrine cells and affect receptors located on ganglion cells.
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PMID:Inner plexiform circuits in the carp retina: effects of cholinergic agonists, GABA, and substance P on the ganglion cells. 617 85

An account is given of the authors' work with isolated adrenal chromaffin cells to study the synthesis, storage and release of catecholamines and of a number of neuropeptides endogenous to the adrenal medulla. A review of other studies in the literature with the isolated chromaffin cell system is included. It is seen that the isolated chromaffin cells are a convenient in vitro system well-suited to studies of basic release mechanisms. The isolated adrenal chromaffin cells maintain high levels of catecholamines and opiates and release them by exocytosis. The cells have both nicotinic and muscarinic receptors but only the nicotinic are involved in the agonist-evoked release of catecholamines (EC50 nicotine 5 X 10(-6) M: ACh 5 X 10(-5) M). The cells can synthesize AChE and selectively release the 10S molecular form by a mechanism different from exocytosis. Substance P (SP) modulates the secretion of catecholamines and ATP evoked by ACh or nicotine but not that evoked by K+ or veratridine. SP appears to interact with the nicotinic receptor-ionophore complex to regulate Na+ entry. SP receptors on the chromaffin cells show similar structural requirements to SP receptors in other SP responsive tissues. Binding studies on isolated chromaffin cell membranes with [4-3H-Phe]SP have shown specific binding in the nM range. In addition, at high concentrations of ACh, SP protects against nicotinic receptor desensitization. Since SP is contained in the splanchnic nerve terminals that innervate the medulla, the demonstration of SP action and SP receptors on the chromaffin cells suggests a physiological role for SP in the regulation of secretion from the adrenal medulla. Somatostatin (SS) and a number of SS analogues also inhibit release, but are approximately 15-fold less potent than SP. Leu- and Met-enkephalin, which are co-stored with adrenaline in the bovine adrenal medullary cells produce a non-specific inhibition of the nicotine-evoked release of CA, but enhance the basal release of endogenous catecholamines by a mechanism that is Ca2+-dependent, stereospecific and reversible by naloxone and naltrexone. The implication of these peptide-amine interactions for physiological processes regulating homeostasis in the adrenal are discussed.
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PMID:Use of isolated chromaffin cells to study basic release mechanisms. 618 74

Patch-clamp techniques were used to examine the effect of substance P on acetylcholine-induced current in bovine chromaffin cells. Cells had been enzymatically isolated and kept in short-term culture. Experiments were performed at 22 degrees C. Under whole-cell voltage-clamp conditions substance P alone (2-10 microM) did not induce ionic currents. Acetylcholine (ACh, 20 microM) at -60 mV induced an inward current that desensitized in the continued presence of ACh. The time course of desensitization was somewhat variable from cell to cell. In most cases it could be fitted by a single exponential with time constant of 8-10 s. Substance P (2-50 microM) applied simultaneously with ACh induced what appeared to be an acceleration of the desensitization process. The time course in the presence of 10 microM-substance P (20 microM-ACh) was best fitted by the sum of two exponentials with time constants of 0.6 s and 5 s respectively. The effect was reversible. The recovery of ACh-induced current from desensitization was not affected by substance P. The time constant for recovery was approximately 7 s in the presence or absence of substance P. Single-channel records showed that the conductance of individual channels was not changed by substance P. The mean open time of single channels was shortened by substance P both at high (20 microM) and at low (0.5 microM) concentrations of ACh. The inverse mean open time varied linearly with substance P concentration. Single-channel responses appeared in bursts and clusters after almost complete desensitization at 20 microM-ACh, as was previously observed in frog skeletal muscle. Substance P dramatically reduced ACh current by increasing interburst intervals while decreasing burst duration and the number of openings per burst. We conclude that substance P inhibits ACh-induced depolarization of chromaffin cells either by increasing the rate of desensitization or by inducing channel blockade, which indirectly enhances desensitization. Possible models of desensitization in the absence and presence of substance P are discussed.
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PMID:Substance P reduces acetylcholine-induced currents in isolated bovine chromaffin cells. 620 May 95

The tripeptides SD-34 and SD-25 induced atropine-, guanethidine-, antihistaminics-resistant but naloxone-sensitive contractions of isolated rat distal colon. They appeared to act on an opioid receptor, probably of the mu subtype, distinct from those for methionine enkephalin and morphine, because the pA2 values of naloxone for the peptides were similar to those for mu-agonists but different from those for methionine enkephalin and morphine, and because the peptides caused contractions of colon that had been desensitized to morphine. Mr 2266, a supposed kappa-antagonist, inhibited the actions of the peptides, ethylketocyclazocine and dynorphin at concentrations much lower than those inhibiting the actions of methionine enkephalin and morphine. Thus these peptides seem to act on the mu- and/or kappa-receptors. The actions of the tripeptides were inhibited by methysergide and methylergometrine, but not by the 5-HT2 antagonist ketanserin, and were not affected by 5-HT or substance P autodesensitization . Thus their actions do not seem to involve 5-HT, histamine, ACh or substance P. It seems likely that the tripeptides, through opioid receptors, directly activate the muscle, or remove some inhibitory modulation of myogenic activity, thus causing contractions.
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PMID:Tripeptides acting on opioid receptors in rat colon. 620 30

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


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