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 mechanisms underlying the regulatory influence of neuropeptide Y (NPY) and of alpha 2-adrenoceptor and opiate receptor activation on cholinergic and excitatory non-adrenergic, non-cholinergic (e-NANC) neurotransmission were studied in guinea pig hilus bronchi in vitro. NPY inhibited both the cholinergic and e-NANC bronchial contractions evoked by field stimulation. The NPY attenuation of the e-NANC contraction could not be antagonized by the alpha 2-antagonist, idazoxan, or naloxone. UK 14,304 a specific alpha 2-agonist, also reduced the two nervous components of bronchial contraction and this action was inhibited by idazoxan. NPY and UK 14,304 exerted a minor influence on the bronchial smooth muscle tone per se or on contractions evoked by acetylcholine or neurokinin A. This suggested that the inhibitory responses were caused by a prejunctional action reducing the release of transmitter substances from sensory and cholinergic nerve endings. Furthermore NPY (10(-7) M) seemed to be more potent to inhibit both contractile components than noradrenaline (10(-6) M) in the presence of propranolol (3 X 10(-6) M). Morphine was able to reduce the e-NANC response via a naloxone-sensitive mechanism. The capsaicin-evoked bronchoconstriction and the bronchodilator NANC effect evoked by field stimulation were, however, not influenced by UK 14,304. It is concluded that NPY, alpha 2-receptor and opiate receptor activation inhibit the release of sensory transmitters evoked by field stimulation but not by capsaicin.
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PMID:Inhibition of cholinergic and non-adrenergic, non-cholinergic bronchoconstriction in the guinea pig mediated by neuropeptide Y and alpha 2-adrenoceptors and opiate receptors. 254 61

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

Morphine and ethylketocyclazocine inhibited neurogenic plasma extravasation (NPE) elicited by antidromic stimulation of the saphenous nerve of the rat. The inhibitory effects of the opiate agonists were antagonised by naloxone and N-methyl nalorphine and independent of any local anaesthetic actions since inhibition of NPE was observed on superfusion of the saphenous nerve with lignocaine, but not with morphine or ethylketocyclozocine. The opiate agonists also failed to inhibit extravasation induced by intradermal administration of substance P. The findings support the contention that specific opioid receptors are located on the peripheral part of primary afferent neurones and these receptors may contribute significantly to peripherally mediated antinociceptive effects of opioids.
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PMID:Peripheral opioid receptors located on the rat saphenous nerve. 609 1

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

Nanomolar concentrations of neurotensin caused a dose-dependent contraction of the longitudinal muscle layer of the guinea-pig ileum. The contractile activity of neurotensin was partially blocked by tetrodotoxin or atropine, indicating that a component of the neurotensin-mediated contraction is indirect in nature and likely involves the release of endogenous acetylcholine from nervous terminals in the myenteric plexus. Dynorphin and related peptide fragments also blocked in part the neurotensin contraction; the potency of this opioid peptide was about the same as that of atropine. Other peptides and alkaloids tested for ability to block the neurotensin contractures included the enkephalins, beta-endorphin, normorphine and the ketocyclazocines; all these opioids inhibited in a dose-dependent fashion the neuronal component of the excitatory effect of neurotensin. The potency of these compounds to reduce the contractions of neurotensin showed good correlation with the potency of these agents to depress by 50% the electrically evoked neuromuscular twitches in the same tissue (r = 0.99); in these tests dynorphin was found to be the most potent of the endogenous opioid-like peptides. The dynorphin blockade was selective to the excitatory effect of neurotensin because the opioid peptide did not antagonize the contractile action of acetylcholine, histamine, substance P, angiotensin II, bradykinin, Ba++ or K+ ions. In addition, somatostatin, vasointestinal peptide, gastrin or adenosine did not modify the potency of neurotensin whereas thyrotropin releasing hormone and epinephrine caused a modest doubling of the neurotensin EC50. The inhibitory action of dynorphin was reduced in the presence of naloxone, suggesting that the interaction involved opiate receptors. Morphine tolerance was not extended to the inhibitory action of dynorphin as evidenced by the finding that the potency of dynorphin-(1-13) to block the neurotensin responses was increased after chronic morphine exposure. In contrast, the potency of dynorphin-(1-13) was significantly reduced in tissues rendered tolerant to the action of ketocyclazocine or ethylketocyclazocine, suggesting that the action of dynorphin could be partially mediated via occupation of K-opiate receptors. Thus, a cholinergic-neuronal component activated by neurotensin on the myenteric plexus appears to be under the inhibitory influence of opiate receptors, suggesting that dynorphin may play a role in the modulation of cholinergic synapses on the enteric nervous system.
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PMID:Dynorphin inhibition of the neurotensin contractile activity on the myenteric plexus. 614 Dec 81

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

A nociceptive stimulus (e.g., foot pinch) produced a significant increase in firing in cells in the nucleus reticularis gigantocellularis (NRGC) and surrounding areas of the rat brain. Substance P (SP), a putative nociceptive neurotransmitter, infrequently produced an increase in spontaneous neuronal firing when administered micro-iontophoretically to these areas. These data indicate that the NRGC is an area involved in nociception. However, SP does not appear to be the primary nociceptive neurotransmitter or neuromodulator in the NRGC because SP did not mimic or enhance the response to the nociceptive stimulus. Morphine (MS) and methionine-enkephalin (ENK), administered microiontophoretically, rarely had any effect on spontaneous neuronal firing or rarely modified the increase in neuronal firing evoked by the nociceptive stimulus. For this reason, the NRGC is apparently not an area where MS and ENK act directly to produce analgesia.
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PMID:Substance P, morphine and methionine-enkephalin: effects on spontaneous and evoked neuronal firing in the nucleus reticularis gigantocellularis of the rat. 615 55

Spinal cords of rats, cats and monkeys were transected; the animals were perfused at varying times. Other rats were injected with morphine and perfused 10 days later. Immunocytochemistry shows substance P (SP) present in control animals primarily in the substantia gelatinosa (SG) of the dorsal horn of the spinal cord. Slight SP immunoreactivity is found in the ventral horn and near the central canal. Starting a few days after transection, there is a buildup of reaction product in the dorsal horn, in sections cut from below the lesion; staining above remains the same. With time, after chordotomy, SP immunoreactivity appears in fibers in lamina V, only in sections below the lesion. Leu-enkephalin (LE) is also found in the SG, however, it is also present in quantity in the ventral horn and central canal areas. Chordotomy has no effect on its distribution indicating LE is intrinsic in the cord and probably contained within interneurons. Morphine increases SP immunoreactivity in the SG, laminae I, IV and V, and in the ventral horn, suggesting morphine analgesia is due to inhibition of intraneuronal SP release in regions specifically associated with pain--SG and lamina V.
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PMID:Substance P and leucine-enkephalin changes after chordotomy and morphine treatment. 616 70

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

The effect of substance P and morphine on the 6-hydroxydopamine (6-OHDA) induced alteration of the postnatal development of central noradrenaline (NA) neurons in the rat has been investigated using neurochemical techniques. Neonatal administration of 6-OHDA systemically leads to permanent NA denervations of distant NA projections, while the projections close to the NA cell bodies are increased, leading to NA hyperinnervation. Intracisternal injection of substance P was found to counteract both the NA denervation and hyperinnervation induced by 6-OHDA. The effect of substance P disclosed a clear dose-dependent relationship. Morphine, on the other hand, was observed to potentiate the alterations induced by 6-OHDA, both the NA denervation and hyperinnervation. The effect of morphine was dose-dependent and could be blocked by the morphine antagonist naloxone. The present results give further support for the view that the 6-OHDA induced alteration of the postnatal development of central NA neurons is related to a "pruning effect." The data furthermore imply that the end-result from a 6-OHDA induced degeneration of central NA neurons during ontogeny may be modulated by the functional state of the neurons.
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PMID:Modulation of 6-hydroxydopamine induced alteration of the postnatal development of central noradrenaline neurons. 618 33


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