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)

The effect of a potent opioid agonist, [D-Met2, Pro5]-enkephalinamide was investigated on two responses involving capsaicin-sensitive afferent neurones, namely, atropine-resistant contractions of the guinea-pig bronchus evoked by electrical field stimulation and the nociceptor stimulation to intraarterial injections of acetylcholine or capsaicin into the vascularly isolated rabbit ear. The hypotheses to be tested were whether (a) opioid receptor activation may inhibit mediator release from primary afferent neurones and (b) the opioid could exert an analgesic effect at a peripheral site of action. Non-cholinergic contractions of the guinea-pig isolated main bronchi due to electrical stimulation were concentration-dependently inhibited by [D-Met2, Pro5]-enkephalinamide (10 nM-1 microM). This effect was abolished by naloxone (1 microM). Naloxone alone induced no change in the stimulation-evoked contractions of the bronchus, indicating that no endogenous opioid control was present. Substance P and neurokinin A induced bronchial contractions that were not influenced by [D-Met2, Pro5]-enkephalinamide. This indicates that [D-Met2, Pro5]-enkephalinamide inhibits electrically-evoked bronchial contractions by reduced mediator release from capsaicin-sensitive sensory nerve endings, since these contractions are most probably brought about by tachykinins, released from afferent neurones. Capsaicin-induced bronchial contractions were in contrast to electrical stimulation not influenced by [D-Met2, Pro5]-enkephalinamide which suggests a different site of action. The activation of sensory neurones in the rabbit ear by i.a. injection of acetylcholine and capsaicin was not reduced under infusion of [D-Met2, Pro5]-enkephalinamide (1 and 10 microM) or lofentanil (1 and 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral effects of opioid drugs on capsaicin-sensitive neurones of the guinea-pig bronchus and rabbit ear. 368 97

A method for assessing inflammatory pain response was developed by modification of the formalin test. Formalin (0.5%, 25 microliters) was injected into the hindpaw of the mouse, and the durations spent in licking or biting response were measured as an indicator of pain response. The response curve was biphasic, having two peaks, from 0 to 5 min (first phase) and from 15 to 20 min (second phase). Morphine, ethylketocyclazocine, ketocyclazocine and pentazocine inhibited the response dose-dependently at the first and the second phases. Aspirin, oxyphenbutazone and dexamethasone inhibited only the second phase. Aminopyrine and mefenamic acid which acted at both central and peripheral sites inhibited both phases; however, the inhibition of the second phase was stronger than that of the first phase. Substance P (SP) antagonist inhibited only the first phase. Bradykinin (BK) inhibitor caused a inhibition of both first and second phases, and pretreatment of compound 48/80 and indomethacin inhibited only the second phase. From these facts, it was suggested that SP and BK played a role in the pain response at the first phase, and histamine, BK and PG were involved at the second phase. Naloxone produced hyperalgesia and bestatin produced analgesia at the second phase; then, it seems that the endogenous opioid system is activated by formalin stimulation and modulates the pain perception. Based on these findings, it is presumed that the pain of the first phase is evoked by the direct stimulation of the nerve fibers, and that of the second phase is due to the inflammatory reaction.
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PMID:[Studies of inflammatory pain response: related pain producing substance and endogenous opioid system]. 372 60

In the rat superior mesenteric arteries, the mechanical responses to perivascular nerve stimulation were characterized. The predominant response was contraction mediated by the release of norepinephrine, acting postjunctionally on alpha 1-adrenoceptors. These frequency-dependent contractions were unaffected by the alpha 2-selective adrenoceptor antagonist yohimbine, but were markedly attenuated by clonidine, the alpha 2-selective adrenoceptor agonist. In the presence of prazosin, the alpha 1-selective antagonist, a significant component of the nerve-mediated contraction was still present. At the concentrations used, prazosin, yohimbine, as well as clonidine acted as competitive antagonists of response to exogenous norepinephrine. This differential inhibition of norepinephrine- and nerve-mediated responses suggested the presence of distinct postjunctional adrenoceptors. The effects of clonidine and yohimbine are interpreted to arise from prejunctional modulation of norepinephrine release. In 30 of the 100 vessels studied, there was spontaneous myogenic tone. In these arteries, field stimulation caused frequency- and voltage-dependent relaxations. These responses were neural in origin, dependent on sympathetic nerve activity, but were nonadrenergic and noncholinergic in nature. Naloxone, indomethacin, and substance P inhibited these relaxations with no significant effect on the tone. The opioid agonist, 1-13 dynorphin relaxed these vessels and only naloxone inhibited this response. The effects of these agents were selective against field-stimulated responses since they did not alter the relaxation to the nonspecific agent sodium nitroprusside. These results provide circumstantial evidence for opioid-mediated vascular relaxation that is presynaptically modulated by prostanoids and substance P.
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PMID:Neurogenic dilatation and constriction of rat superior mesenteric artery in vitro: mechanisms and mediators. 375 25

The putative peptide neurotransmitter cholecystokinin (CCK) is co-localized with substance P (SP) in a dense cluster of neurons located in the rat Edinger-Westphal (EW) nucleus. In an attempt to record electrophysiologically from these CCK-containing neurons, we have identified a group of nociceptive neurons located within the confines of the EW nucleus. The firing pattern of these nociceptive neurons is erratic, sometimes with a bursting pattern and at other times with fairly regular rates which vary generally from 1 to 7 Hz. These neurons respond to noxious stimuli, such as toe pinch, with an increase in rate and sometimes enter an apparent depolarization blockade (preceded by an increase in the duration and a decrease in the amplitude of the action potential). Systemically administered morphine suppresses both the spontaneous firing rate and the toe pinch-induced increase in firing rate. Naloxone is able to reverse the effects of morphine. Although we have identified in the EW area a moderate density of terminals containing enkephalin-like immunoreactivity, morphine locally applied via microiontophoresis is largely without effect on the firing of these neurons. We hypothesize that the opiate-induced suppression of these nociceptive neurons is not mediated directly on the EW cells, but rather indirectly through afferent systems.
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PMID:Cholecystokinin-containing and nociceptive neurons in rat Edinger-Westphal nucleus. 394 95

This study describes effects of various peptides, neurotransmitters and cyclic nucleotides on brain polyphosphoinositide metabolism in vitro. The interconversion of the polyanionic inositol phospholipids was studied by incubation of a lysed crude mitochondrial/synaptosomal fraction with [gamma-32P]-ATP. The reference peptide ACTH1-24 stimulated the formation of radiolabelled phosphatidylinositol 4,5-diphosphate (TPI) and inhibited that of phosphatidic acid (PA). Substance P inhibited both TPI and PA labelling, whereas beta-endorphin inhibited that of PA without any effect on TPI. Morphine had no effect at any concentration tested, whereas high concentrations of naloxone inhibited the labelling of both PA and TPI. Naloxone did not counteract the effects of ACTH1-24. The other peptides tested (lysine 8-vasopressin and angiotensin II) were without any effect. Under the conditions used, adrenaline, noradrenaline and acetylcholine did not affect the labelling of the (poly)phosphoinositides. Both dopamine and serotonin, however, dose-dependently inhibited the formation of radiolabelled TPI and PA. Low concentrations of cAMP stimulated TPI, but higher concentrations had an overall inhibitory effect on the labelling of TPI, PA and especially phosphatidylinositol 4-phosphate (DPI). The cyclic nucleotide did not mediate or counteract the effects of ACTH, and cGMP was without any effect. These results are discussed in the light of current ideas on the mechanism of action of neuropeptides.
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PMID:Polyphosphoinositide metabolism in rat brain: effects of neuropeptides, neurotransmitters and cyclic nucleotides. 612 17

Multibarrelled microelectrodes were used to test the effects of iontophoretically released substance P (SP), morphine, glutamate, and naloxone on spinal cord dorsal horn neurons. Cells excited by SP were also excited by noxious stimuli, a finding consistent with the hypothesis that SP is the neurotransmitter released by primary nociceptor afferents to excite dorsal horn neurons. Iontophoretic morphine failed to depress the SP-induced discharges. Indeed, iontophoretic morphine frequently potentiated the SP responses. In addition to potentiating SP-induced discharges, iontophoretic morphine frequently increased both the spontaneous activity of dorsal horn neurons and the activity evoked in these cells by noxious cutaneous heat and iontophoretic glutamate. Naloxone did not antagonize these excitatory effects. Intravenous morphine only depressed spontaneous discharges. Nevertheless, iontophoretic morphine still produced excitatory effects in spinal animals pretreated with analgesic doses of intravenous morphine. It is concluded that such excitatory effects are toxic actions indicative of supratherapeutic morphine concentrations in the vicinity of the neuron being studied. Intravenously administered morphine depressed the spontaneous activity of dorsal horn neurons of spinal cats, but failed to depress their responses to SP. Morphine also failed to antagonize SP's biological effects in peripheral systems (contraction of isolated guinea pig ileum, rabbit hypotensive effect, rat sialogogic response). It is concluded that morphine is not a substance P receptor antagonist. The results are discussed with respect to the hypotheses that (1) the spinal analgesic effects of systemically administered morphine occur on presynaptic terminals of sensory neurons, and (2) an SP antagonist might be a unique analgesic agent.
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PMID:Morphine does not antagonize the substance P mediated excitation of dorsal horn neurons. 615 56

Male Sprague-Dawley rats were trained to discriminate ethanol (2 g/kg, PO: EtOH) from saline (10 ml/kg, PO: SAL) in a two-bar positively reinforced operant task on a VI 15 sec schedule. After the rats reached criterion performance (greater than 90% correct responses on the appropriate lever), thyrotropin releasing hormone (pyroGlu-His-Pro-NH2: TRH), a metabolite of TRH (His-Pro diketopiperazine: HP), and a structural analog of TRH (HPCA-His-ThiaPro-NH2: OHT) were tested for their ability to antagonize the EtOH cue. These peptides were chosen for their reported ability to reverse ethanol-induced narcosis. However, at doses that did not disrupt performance, TRH, HP, and OHT did not affect the stimulus properties of ethanol at any dose tested, nor did they change the stimulus properties of saline. Naloxone and ACTH(1-10)-NH2 were also tested as ethanol antagonists of the training dose. Pretreatment with either of these compounds failed to alter ethanol-appropriate responding. In addition, (DA1a2-Met5)-enkephalin-ol, (DAla2-Met(O)5)-enkephalin-ol, substance P, delta sleep-inducing peptide, and bombesin were tested for their ability to elicit ethanol appropriate responding. The EtOH cue generalized to none of these peptides.
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PMID:The effects of peptides on the stimulus properties of ethanol. 615 98

The putative transmitters, enkephalins and substance P, and their binding sites have been identified in the nucleus of the solitary tract. Their role in the modulation of baroreceptor reflex activity is the subject of this study in the rabbit. A stable decarboxy analog of leu-enkephalin, RX 783016, which has mu receptor specificity, was used to attenuate the baroreflex sensitivity to intravenous phenylephrine. RX 783016, 50 micrograms/kg intracisternally, did not alter resting heart rate of blood pressure. Intravenous administration of the opiate receptor antagonist, naloxone, prevented the effects of RX 783016. Naloxone given alone significantly increased reflex sensitivity. Substance P given intracisternally in low doses (1 to 10 ng/kg) caused a dose-dependent pressor response, which was reduced by pretreatment with morphine and enhanced by naloxone. Bilateral sinoaortic denervation also enhanced the pressor response to substance P, but after deafferentation, naloxone had no further effect. It is proposed that enkephalin-containing neurons, acting through mu receptors, and substance P neurons influence baroreceptor reflex activity by modulating respectively the primary and second order neurons of the baroreceptor reflex.
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PMID:Opiate analogs, substance P, and baroreceptor reflexes in the rabbit. 616 14

1 Experiments were carried out to determine whether opiates and opioid peptides could affect noncholinergic excitatory responses of the isolated guinea-pig ileum. 2 Transmural field stimulation (10-20 Hz) of an atropine pretreated, intact segment of gut produced a contracture that could be elicited repeatedly without significant variation in magnitude. 3 This noncholinergic contracture was significantly reduced 75.3 +/- 8.3% (mean +/- s.e. mean) by tetrodotoxin (TTX; 1 microgram/ml) and by desensitizing the preparation to substance P (76.3 +/- 10.1%). 4 Morphine (5 x 10(-6) M) as well as the opioid peptides D-Ala2, N-Phe4, Met-(0)-01 (FK 33-824; 9 x 10(-7) M), D-Met2-Pro5 enkephalin (3 x 10(-7) M) and D-Ala2-D-Leu5-enkephalin (5 x 10(-6) M) inhibited the magnitude of the noncholinergic contracture but did not alter contractile responses to exogenous substance P (4 x 10(-11) M--4 x 10(-10) M). 5 Pretreatment with the nicotinic receptor blocker, hexamethonium (10(-5)--10(-4) M) reduced by about 35% the magnitude of the atropine-resistant contracture but did not affect inhibitory responses to morphine or opioid peptides. Thus the inhibition produced by morphine on the 20 Hz contracture does not involve a nicotinic cholinergic mechanism. 6 Naloxone pretreatment (10(-6) M) in the presence of hexamethonium (10(-5)--10(-4) M) enhanced the magnitude of the noncholinergic contracture without affecting responses to exogenous substance P (4 x 10(-11)--4 x 10(-10) M). 7 These data suggest that substance P is the main, if not the sole, mediator of the atropine-resistant 20 Hz contracture and indicate further that exogenous as well as endogenous opioids can modulate the release of this enteric peptide.
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PMID:Effects of opioids on noncholinergic excitatory responses of the guinea-pig isolated ileum: inhibition of release of enteric substance P. 617 87

Naloxone causes a tonic contraction (= "gut dependence") of the ileum in morphine-dependent rats. This "gut dependence" can be antagonized by morphine (2.5 X 10(-7) g/ml). Substance P-undecapeptide (SP1-11) produces a tonic contraction of the ileum in morphine-independent rats and also in morphine-dependent rats. In the latter, this tonic contraction is comparable with the naloxone-induced contraction. When morphine-dependent rats with naloxone-induced "gut dependence" are given SP1-11, they show an additional increase in tonus followed by a rapid tonus inhibition. Substance P-heptapeptide (SP5-11) also causes a naloxone-like contraction in both the morphine-dependent and the morphine-independent rats. In contrast to SP1-11, SP5-11 produces neither a tonus superposition nor a tonus inhibition in morphine-dependent rats with naloxone-induced "gut dependence". The fact that SP5-11 does not, in contrast to SP1-11, exert these two effects (tonus superposition and subsequent tonus inhibition) is indicative of differences between the mechanisms of the two Substance P sequences.
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PMID:[Differences in activity between substance P and substance P-heptapeptide as studied on the phenomenon of "gut dependence" in rats (author's transl)]. 618 Apr 43


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