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 intracellular adenine nucleotide pool of rabbit iris-ciliary body was labelled by uptake of 3H-adenine in vitro. A variety of agents were tested for their ability to stimulate or inhibit the incorporation of radioactivity into cyclic AMP formed from ATP labelled with 3H-adenine. Isoproterenol, vasoactive intestinal peptide, forskolin, and prostaglandin E2 stimulated incorporation of label 3-10-fold in 15-20 min compared with paired tissues not treated with hormone, whereas histamine, serotonin, substance P, and bradykinin were inactive. Clonidine, alpha-methylnorepinephrine, and dopamine decreased the rate of incorporation of label into the cyclic-AMP pool in tissues that showed high spontaneous basal rates. In low-basal tissues these drugs were inactive by themselves but clonidine and alpha-methylnorepinephrine blocked the stimulation effected by isoproterenol. The findings indicate that several receptor-coupled adenylate cyclase systems are present in ICB and that dual adrenergic control of adenylate cyclase through positive and negative coupling of adrenergic receptors probably occurs. The negatively coupled adrenergic receptors appear to be similar to the alpha 2-subclass of adrenergic receptor described in other tissues. These observations suggest a role for the large number of alpha 2-adrenergic-binding sites found in albino rabbit iris-ciliary body by ligand binding assays.
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PMID:Drug responses of adenylate cyclase in iris-ciliary body determined by adenine labelling. 298 54

A variety of pharmacological agents were used as experimental probes to determine with greater precision the site(s) of damage to cerebral adenylate cyclase as a consequence of postischemic reperfusion in the gerbil. A paradigm of 60-min bilateral ischemia followed by 40-min reperfusion results in a decreased sensitivity of the catalytic site of adenylate cyclase to Mn2+. Likewise, the GTP-transducer site (guanine nucleotide regulatory or G protein) revealed depressed responses to GTP in the absence or presence of norepinephrine, dopamine agonists, substance P, yohimbine, and cholera and pertussis toxins. Moreover, a crude preparation of GTPase disclosed that damage elicited by postischemic reperfusion was directed to the higher-affinity form of this enzyme, which is associated with the overall function of the guanine nucleotide regulatory protein. Injury to adenylate cyclase was unrelated either to the ability of adrenergic ligands to bind to associated receptor sites or to the capacity of the brain to generate visual evoked potentials in response to visual stimuli.
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PMID:Further probes into the molecular sites of damage to cerebral adenylate cyclase following postischemic reperfusion. 310 40

Some biochemical factors of the iris-ciliary body of the rabbit have been examined for effects induced by water-soluble marihuana-derived material (MDM). Adenylate cyclase activity and sensitivity to beta-adrenergic agonists were unchanged, as measured 4 hours after MDM administration in vivo. Magnesium-dependent and anion-sensitive, but not sodium-potassium, ATPase activities were inhibited 6 hours after MDM administration in vivo, although they were unaffected by in vitro incubation. Topical administration of a potent substance P antagonist had no effect on the time course or magnitude of intravenous MDM-induced ocular effects in rabbit. Intravenously administered sugars antagonized the effects of MDM on intraocular pressure. A variety of drugs which display a range of biochemical effects varying from beta-adrenergic receptor agonism, to alteration of glycoprotein residues were employed. None of the agents employed, ranging from cAMP modifiers to protein synthesis blockers, had any effect on the MDM-induced response. It is apparent that the mechanism underlying the ocular hypotensive effect of MDM does not reside in mediation through adenylate cyclase, ATPase or substance P, but rather through a mechanism mediated by terminal sugar moieties on the molecule. The data suggest that modification of the surface membrane glycoprotein residues on the ciliary epithelium can induce marked alterations in aqueous humor flow rate.
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PMID:Marihuana-derived material: biochemical studies of the ocular responses. 316 May 44

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)
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PMID:Calcitonin gene-related peptide and tachykinins in relation to local sensory control of cardiac contractility and coronary vascular tone. 326 56

The onset of therapeutic effectiveness of carbamazepine is generally very rapid in the treatment of seizure and paroxysmal pain disorders, shows some lag in the treatment of mania, and exhibits the longest lag in depression. These time course variations may indicate that different mechanisms underlie the efficacy of carbamazepine in the differential neuropsychiatric syndromes. Biochemical and pharmacological data suggest that the anticonvulsant effects of carbamazepine are related to "peripheral-type" benzodiazepine and alpha 2-noradrenergic receptor systems and to its ability to stabilize sodium channels. GABAB (baclofen-like) actions appear to be involved in antinociceptive, but not anticonvulsant, effects. The relatively acute time course of antimanic efficacy may be related to the above-mentioned mechanisms or to other effects related to systems postulated to be altered in the manic syndrome. These effects might include carbamazepine's ability to increase acetylcholine in the striatum, decrease probenecid-induced levels of CSF homovanillic acid (HVA) in man and dopamine turnover in animals, decrease CSF norepinephrine in manic patients, inhibit adenylate cyclase activity (in response to norepinephrine, dopamine, adenosine, or ouabain), decrease GABA turnover, or act as a vasopressin agonist. Efficacy in depression may be related to actions in man that take time or chronic drug administration to develop, such as increases in plasma tryptophan, decreases in CSF somatostatin, decreases in thyroid indices, and increases in urinary free cortisol excretion and, in animals, increases in substance P sensitivity and increases in brain adenosine receptors. The ability of carbamazepine to block the development of lidocaine- and cocaine-induced seizures also requires chronic administration, suggesting that these seizure models may provide a unique perspective for understanding mechanisms of time-dependent effects.
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PMID:Time course of clinical effects of carbamazepine: implications for mechanisms of action. 328 May 60

1. The biogenic amines 5-hydroxytryptamine (5-HT) and histamine, and the peptides bombesin, gastrin-releasing peptide (GRP), vasoactive intestinal peptide (VIP), cholecystokinin (CCK), substance P and calcitonin gene-related peptide (CGRP) each mimicked slow synaptic excitation (slow e.p.s.p.) when applied to myenteric neurones of the guinea-pig small intestine. 2. Stimulation of the catalytic activity of adenylate cyclase by forskolin and intraneuronal elevation of cyclic 3',5'-adenosine monophosphate (cyclic AMP) also mimicked the slow e.p.s.p. and the actions of the aminergic and peptidergic messengers. 3. Adenosine prevented stimulation of adenylate cyclase by forskolin and abolished the slow e.p.s.p.-like actions of forskolin. 4. Exposure of the neurones to adenosine prior to or during application of bombesin, GRP, VIP, CCK or histamine blocked the actions of these substances. 5. Pre-treatment with adenosine did not suppress the slow e.p.s.p.-like actions of substance P, CGRP or 5-HT. 6. The results suggest that signal transduction for bombesin, GRP, VIP, CCK and histamine involves stimulation of adenylate cyclase and second messenger function of cyclic AMP. Transduction mechanisms for 5-HT, substance P and CGRP appear not to involve second messenger function of cyclic AMP.
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PMID:Transduction of aminergic and peptidergic signals in enteric neurones of the guinea-pig. 365 77

The isolated guinea pig ileum provides a model in which drug dependence can be induced in normal neurons. The characteristics of opiate dependence in the ileum closely resemble those of dependence in whole animals. Convergent dependence on normorphine, clonidine, and adenosine can be separately induced in the ileum in vitro. Use of selective antagonists indicates that both acetylcholine and substance P participate in the withdrawal response associated with all three of these dependencies. The demonstration that adenosine derivatives suppress opiate withdrawal in the guinea pig ileum and in mice raises the possibility that they might act similarly in man. The point at which the dependencies on normorphine, clonidine, and adenosine converge is probably below their separate recognition sites and is possibly at the level of adenylate cyclase regulation.
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PMID:Sites and mechanisms of dependence in the myenteric plexus of guinea pig ileum. 608 97

The nicotinic acetylcholine receptor of Torpedo californica has been shown to be subject to cyclic AMP-dependent phosphorylation, raising the possibility that nicotinic receptors may be regulatable by phosphorylation. To investigate this possibility for a neuronal nicotinic receptor, we have studied the effects of elevation of cyclic AMP on the ion-conducting properties of the nicotinic receptor of PC12 cells. The cyclic AMP content of the cells was altered by exposure to various concentrations of forskolin (an activator of adenylate cyclase) for periods of time ranging from 1 to 40 min. Receptor activation then was measured as agonist-induced influx of 86Rb+ into the cells. Throughout a variety of conditions, no changes in agonist-induced ion influx were detected. This was true regardless of the concentration of agonist used, the duration of receptor stimulation that was measured, the concentration of forskolin employed, or the duration of elevation of cyclic AMP prior to receptor activation. Experiments designed to measure receptor desensitization also were unable to detect any differences upon elevation of cyclic AMP. Finally, the antagonism of receptor activation by substance P also was not affected by elevation of cyclic AMP. Thus, no evidence could be obtained in these cells supporting the hypothesis that a neuronal nicotinic acetylcholine receptor can be acutely regulated by changes in cellular cyclic AMP.
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PMID:Acute elevation of cyclic AMP does not alter the ion-conducting properties of the neuronal nicotinic acetylcholine receptor of PC12 cells. 608 18

Somatostatin-14 inhibited the isoproterenol-stimulated adenylate cyclase in cell-free homogenates of pituitary intermediate lobe of the male rat with a Ki of 7.25 +/- 0.31 X 10(-7) M. Somatostatin-28 was found to be a partial agonist. Other neuropeptides (met- and leu-enkephalin, beta-endorphin, alpha-melanocyte-stimulating hormone, ACTH, neurotensin, substance P, vasoactive intestinal polypeptide, and vasopressin) were without effect. Our results suggest a role for pituitary and/or brain somatostatin in the physiological regulation of the intermediate pituitary lobe, and the possibility of an interaction between somatostatins and catecholamines on the regulation of intermediate lobe adenylate cyclase.
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PMID:Somatostatin inhibits the isoproterenol-stimulated adenylate cyclase in the intermediate lobe of the male rat pituitary gland. 613 24

With appropriate measures to protect 3H-substance P (3H-SP) from proteolytic degradation and from nonspecific adsorption to glass-fiber filters, we have been able to demonstrate reliably a high-affinity specific binding of 3H-SP to rat submaxillary/sublingual gland membranes with a KD of 1 nM and Bmax of 6 pmoles/g of tissue. The relative potencies of various SP fragments and related analogues in reducing 3H-SP binding parallel their potencies in stimulating phosphatidylinositol turnover, amylase release, and salivation, thus supporting an association of the observed 3H-SP binding site with the physiological SP receptors in this tissue. This binding is selectively stimulated by some divalent cations (Mn2+ greater than Mg2+ greater than Ca2+) but inhibited by several guanyl nucleotides, suggesting a possible linkage to adenylate cyclase. However, no effect of SP on either the basal or the norepinephrine-stimulated adenylate cyclase activity could be demonstrated in salivary gland homogenates.
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PMID:3h-substance P binding to salivary gland membranes. Regulation by guanyl nucleotides and divalent cations. 619 Nov 91


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