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)

Acute intracerebral injection of the undecapeptide, substance P, in mice induced a unique reciprocal hindlimb scratching response whose intensity was dose-related. Similar intracerebral dose-response curves were obtained by the structurally related undecapeptides, physalaemin and eledoisin, but not by several unrelated peptides (TRH, neurotensin, bradykinin, somatostatin), prostaglandins E2 and F2a, dibutyryl cyclic AMP or dibutyrylcyclic GMP. Analgesic narcotic agents with predominant agonist activity administered i.p. prevented the reciprocal hindlimb scratching response induced by intracerebral substance P (0.625 microgram/mouse = ED 95). In this in vivo assay their action was stereospecific and exhibited a rank order of potency similar to that reported for analgesic activity and binding to opiate receptors in vitro. Narcotic agents with mixed agonist-antagonist activity were inactive while the narcotic antagonist, naloxone, completely reversed the action of morphine. Higher doses of naloxone alone potentiated substance P-induced reciprocal hindlimb scratching which may explain why partial narcotic agonists failed to abolish the response. There is now considerable evidence in support of a sensory neurotransmitter/modulator role for substance P within the central nervous system, and one of its actions may be associated with nociception. This concept is supported by observations in the present study which indicate that the substance P-induced reciprocal hindlimb scratching response involves nociceptive pathways within the central nervous system.
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PMID:Intracerebral substance P in mice: behavioral effects and narcotic agents. 616 31

Somatostatin, substance P, cyclic AMP and cyclic GMP were determined in the cerebrospinal fluid of patients with Huntington's disease, in first generation relatives of choreic patients and in neurological control patients. Substance P levels were not significantly altered, but somatostatin levels were markedly decreased both in affected patients and symptom-free offspring. Cyclic AMP was decreased only in patients with advanced stages of the disease while cyclic GMP was normal. Evidence is discussed which may support a role of somatostatin deficiency in the pathophysiology of chorea.
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PMID:Huntington's chorea-- measurements of somatostatin, substance P and cyclic nucleotides in the cerebrospinal fluid. 616 83

Peptide and non-peptide agents were tested for their stimulatory or inhibitory effects on circular strips of guinea pig isolated tracheae. Substance P, eledoisin, physalaemin, neurotensin, angiotensin, histamine and carbachol were found to contract, while noradrenaline, dopamine, bradykinin, nucleotides (AMP, ADP, ATP) and prostaglandins (PGE1, PGE2, PGA2) induced concentration-dependent relaxations of tracheae contracted with substance P or carbachol. Indomethacin (2.8 X 10(-6) M) significantly potentiated the effect of substance P and blocked that of bradykinin. The contractions to substance P of tissues treated with indomethacin were not modified by atropine, methysergide, diphenhydramine, cimetidine, propranolol, phentolamine, [Leu8]-ATII, [Leu8]-des-Arg9-bradykinin, naloxone and baclofen. The order of potency of C-terminal fragments of substance P was: hexa(6-11) greater than hepta(5-11) greater than substance P greater than = octa(4-11). It is concluded that the guinea pig isolated trachea is a pharmacological preparation sensitive to numerous agents and useful for studying structure-activity relationship and the mechanism of cellular action of several peptides, particularly substance P.
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PMID:Pharmacological effects of peptides on tracheal smooth muscle. 618 32

A neuropeptide, substance P (1-50 microM) caused a prompt but transient rise in tissue cyclic AMP levels and also increased the release of thyroid hormones from canine thyroid slices. While norepinephrine markedly inhibited the stimulation by TSH of such parameters as reported previously, substance P had no effect. These results suggest that substance P may play a regulatory role in thyroid gland functions in a manner different from norepinephrine.
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PMID:Effects of substance P on thyroidal cyclic AMP levels and thyroid hormone release from canine thyroid slices. 618 38

Neuropeptides may have functions in the central nervous system (CNS) other than altering neuronal excitability. For example, they may act as regulators of brain metabolism by affecting glycogenolysis. Since it has been suggested that glial cells might provide metabolic support for neuronal activity, they may well be one of the targets for neuropeptide regulation of metabolism. Consistent with this view are reports that peptide-containing nerve terminals have been seen apposed to astrocytes, but it is also quite possible that peptides could act at sites lacking morphological specialization. Primary cultures containing CNS glial cells have been shown to respond to beta-adrenergic agonists with an increase in cyclic AMP and, as a result, with an increase in glycogenolysis and have also been shown to respond to a variety of peptides with changes in cyclic AMP. In the study reported here, we have examined the effects of several peptides on relatively pure cultures of rat astrocytes. We demonstrate that the increase in intracellular cyclic AMP induced by noradrenaline is markedly enhanced by somatostatin and substance P and is inhibited by enkephalin, even though these peptides on their own have little or no effect on the basal levels of cyclic AMP. Vasoactive intestinal peptide (VIP) on the other hand increases cyclic AMP in the absence of noradrenaline. These results suggest that neuropeptides influence glial cells as well as neurones in the CNS and, in the case of somatostatin and substance P, provide further examples of neuropeptides modulating the response to another chemical signal without having a detectable action on their own.
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PMID:Neuropeptides modulate the beta-adrenergic response of purified astrocytes in vitro. 619 28

Adenosine had a dual effect on the IgE-mediated histamine secretion from rat peritoneal mast cells: an inhibition at relatively low concentrations and a potentiation at higher concentrations. An adenosine R-site analog, N6-methyladenosine, had a similar dual effect while adenosine P-site analogs, 9-beta-D-arabinofuranosyladenine and 2'-deoxyadenosine, had neither inhibitory nor potentiating effects. Both compound 48/80- and alpha-chymotrypsin-induced histamine secretion were dose-dependently inhibited by adenosine. Not only R- and P-site analogs of adenosine but also a wide variety of purine and pyrimidine derivatives such as adenine, AMP, cyclic AMP, ADP, guanosine, inosine and cytosine showed inhibitory activities on the compound 48/80-induced histamine secretion. Adenosine had no influence on substance P- and neurotensin-induced histamine secretion.
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PMID:Differential effects of adenosine on histamine secretion induced by antigen and chemical stimuli. 619 35

The mechanism underlying the positive inotropic and chronotropic effects of capsaicin were investigated using the spontaneously beating guinea-pig atrium in vitro. Capsaicin induced a long-lasting stimulatory effect (threshold dose 10(-9) M). Tetrodotoxin, phentolamine, 6-OHDA, mepyramine plus cimetidine, methysergide-, indomethacin-, somatostatin- or morphine pretreatment and local treatment with capsaicin on the vagal nerves did not reduce the capsaicin response, while it was abolished up to 1 month after systemic capsaicin pretreatment. The capsaicin response was subject to a rapid tachyphylaxis. During capsaicin tachyphylaxis, the positive inotropic and chronotropic effects of noradrenaline, serotonin and histamine were unchanged. Various neuropeptides were investigated with regard to cardiac activity. Physalaemin, eledoisin and somatostatin had negative inotropic and chronotropic effects. Substance P, bombesin, kassinin, CCK-8 or PHI (up to 10(-6)M of each) did not cause any detectable response on the guinea-pig auricle, while the substance P antagonist [D-Arg, D-Pro, D-Trp, Leu]SP induced a long-lasting stimulation of heart activity, VIP also stimulated the heart. Various adenyl compounds were also tested. Adenosine, AMP, ADP, ATP and beta-, gamma-methylene ATP had negative chronotropic and inotropic effects, while alpha-, beta-methylene ATP induced a stimulatory response. During alpha-, beta-methylene ATP tachyphylaxis, the auricles still responded to capsaicin. The inhibitory effects of adenosine and ATP analogues were antagonized by theophylline and 8-p-sulfophenyl theophylline. Capsaicin induced a small release of labelled nucleotides from 3(H)-adenine-prelabelled atria from control, but not from capsaicin-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Capsaicin-induced stimulation of the guinea-pig atrium. Involvement of a novel sensory transmitter or a direct action on myocytes? 620 51

Adenosine 5'-triphosphate (ATP), substance P (SP) and non-cholinergic nerve stimulation contracted the guinea-pig urinary bladder. SP and two poorly-degradable analogues of ATP, the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP and L-AMP-PCP), were used to desensitize the guinea-pig bladder. Desensitization of the bladder by AMP-PCP (50 microM) or by L-AMP-PCP (50 microM) abolished the responses to ATP, and inhibited the responses to non-cholinergic nerve stimulation and to SP. The responses to histamine were unaffected. Desensitization by SP (1 microM) inhibited the responses to SP itself, but not the responses to ATP, L-AMP-PCP or non-cholinergic nerve stimulation. These results suggest that SP may act partly by releasing ATP, and support the suggestion that ATP rather than SP is the non-cholinergic stimulatory transmitter.
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PMID:Desensitization of the guinea-pig urinary bladder by the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate and by substance P. 620 88

The effects of the undecapeptide, substance P(SP), on the secretion of mucin and proteolytic enzymes from dispersed cells of the rat submandibular gland were studied. The peptide, at a concentration of 1 X 10(-7) M, stimulated the release of 31.9 +/- 3.0% (mean +/- SEM) of intracellular mucin over 40 min, compared with 12.5 +/- 1.5% in untreated controls (p less than 0.01). This effect was duplicated by the homologous peptides, physalaemin, and eledoisin-related peptide. Substance P action was not affected by pre-incubation of cells with phentolamine or propranolol and was therefore independent of adrenergic stimulation. Furthermore, SP did not enhance the intracellular concentrations of cyclic AMP or cyclic GMP, confirming that cyclic nucleotides were not involved in its stimulus-secretion coupling mechanism. The isoproterenol-stimulated secretion of mucin from dispersed cells was reduced to 75.7% of the normal response (p less than 0.01) after a brief exposure to SP. This inhibitory effect was probably mediated by intracellular events rather than by direct effects on cell surface receptors. However, mucin release after treatment with SP followed by norepinephrine (NE) was 161% of that caused by NE alone (p less than 0.01) and may reflect an additive response to the independent stimulation of SP and NE receptors. Substance P and related peptides had no effect on arginine esterase secretion in the experimental model, although a response was elicited by alpha- and beta-adrenergic agonists. It is, therefore, proposed that serous cells of the granular convoluted tubule in the rat submandibular gland lack substance P receptors.
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PMID:Effect of substance P on exocrine secretion by rat submandibular gland cells. 620 29

Capsaicin (CAP) caused a time, concentration and Ca++ dependent increase in cyclic AMP accumulation in tissue slices from rat and guinea pig spinal cord. The CAP-induced increase occurred uniquely in slices from dorsal cord of both rat and guinea pig and the increase was significantly greater in dorsal cord slices from guinea pig vs rat spinal cord. CAP mediated release of substance P does not appear to mediate the CAP-induced increase in cyclic AMP accumulation since the increase in cyclic AMP is significantly less with substance P and the substance P antagonist [D-Pro2, D-Trp7,9]-substance P does not antagonize the CAP-induced increase. The CAP-induced increase in cyclic AMP accumulation appears to be a direct effect. Structural requirements for this effect are both the substituted aromatic and alkyl side chain portion of the CAP molecule. The present results suggest that CAP has the ability to interact with sites in dorsal spinal cord which are linked to the synthesis of cyclic AMP, which could modulate spinal processing of nociceptive information.
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PMID:Comparison of capsaicin and substance P induced cyclic AMP accumulation in spinal cord tissue slices. 620 38


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