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)

Histamine was released from mast cells in isolated perfused heart and kidney of the rat, but not from mast cells in guinea-pig tissues, by a substance P (SP) analogue (SP(1-4)-NH-C12H25), SP(1-4)-C12 for abbreviation. This peptide also released histamine from peritoneal mast cells and basophil leucocytes of the rat. Substance P itself was compared with SP(1-4)-C12 and some structurally related peptides and showed weaker activity. SP(1-4)-C12 also released leukotrienes C4, D4, E4 and thromboxane B2 from rat heart. However, there was little effect on heart rate and force of contraction and no effect on perfusion pressure (vascular resistance) of either rat heart or kidney. The findings demonstrate the structural requirements for histamine release by SP (a possible mediator of 'neurogenic' inflammation), the metabolic energy-dependence of the release process and the functional heterogeneity and interspecies differences in mast cell populations.
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PMID:Substance P and Arg-Pro-Lys-Pro-NH-C12-H25-induced mediator release from different mast cell subtypes of rat and guinea-pig. 247 Jun 97

In epicardial conduit coronary artery strips obtained during autopsy within 2.5 h after death, relaxations induced by low concentrations of histamine were reversed to contractions by removal of endothelium, whereas those caused by bradykinin, substance P, and Ca2+ ionophore A23187 were almost abolished. In the artery strips with intact endothelium, which responded to histamine, bradykinin, and substance P with moderate or marked relaxations, acetylcholine elicited contractions. Endothelium denudation failed to potentiate the contractile response to acetylcholine and serotonin. Relaxant responses to histamine, bradykinin, and substance P did not significantly differ in coronary arteries from adults (35-48 yr old) and seniors (63-82 yr old). Two strips from a 2-mo-old male responded to acetylcholine only with contractions, and their responses to the vasodilators were not greater than those seen in the adult and senior arteries. Histamine increased guanosine 3',5'-cyclic monophosphate (cGMP); the increments did not differ in the arteries from adults and seniors. It may be concluded that endothelium is a major site for relaxant actions of histamine, bradykinin, and substance P, whereas muscarinic receptors, if any, in endothelium do not play an important role in the generation of relaxing factor from human coronary arteries. The endothelium-dependent relaxations do not appear to be altered with increasing age or in the arteries with slight atherosclerotic changes.
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PMID:Endothelium-dependent and -independent responses to vasoactive substances of isolated human coronary arteries. 247 41

The involvement of cholinergic and C-fibre mediated mechanisms in the stimulation of mucociliary activity induced by prostaglandins and histamine was investigated in vivo in the rabbit maxillary sinus with a photoelectric technique. The prostaglandins E, (PGE,) and F2(2) alpha (PGF2 alpha) in dose of 0.1 microgram/kg and 10 micrograms/kg respectively stimulated the mucociliary activity in a biphasic fashion, with a small initial response during the first 1-2 min and a later maximum response after 3-4 min. These effects were resistant to atropine and to the SP antagonist (D-Pro2, D-Trp7,9)SP. The small initial response was blocked by pretreatment with high doses of capsaicin (13 mg i.a.), while the maximum response was unaffected. This indicates that the mucociliary responses induced by PGE, and PGF2 alpha involve capsaicin-sensitive C-fibres but that neither acetylcholine nor substance P were responsible. Histamine (50 micrograms/kg) stimulated mucociliary activity in the rabbit maxillary sinus and the effect was abolished by pretreatment with high doses of capsaicin and reduced by the SP antagonist (D-Pro2, D-Trp7,9)SP. This indicates that the histamine-induced stimulation of mucociliary activity involves capsaicin-sensitive C-fibres and that the effect might be mediated by substance P.
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PMID:Cholinergic and C-fibre mediated mechanisms in the stimulation of mucociliary activity induced by prostaglandins and histamine. 248 54

We have investigated whether the histamine H3-receptors influence nonadrenergic noncholinergic (NANC) bronchoconstriction in guinea-pig in vivo. Atropine, propranolol, mepyramine and cimetidine were administered to block the effects of beta-adrenoceptor-, acetylcholine, H1- and H2-receptor-mediated responses, respectively. Vagal stimulation evoked a NANC bronchoconstrictor response. The selective H3-agonist, alpha-methylhistamine (alpha-MeHA, 1-10 mg/kg i.v.) did not alter basal respiratory insufflation pressure, but reduced the NANC bronchoconstrictor response to vagal stimulation in dose-dependent manner (with a maximal inhibition of 46.0 +/- 10.3%; mean +/- S.E. at 10 mg/kg) (P less than 0.02). Histamine itself also had a significant inhibitory effect on NANC responses with H1- and H2-blockade. The alpha-adrenoceptor antagonist phentolamine had no effect on the inhibitory response produced by alpha-MeHA, but the H3-receptor antagonist thioperamide blocked the inhibitory effect of alpha-MeHA. alpha-MeHA had no inhibitory effect on bronchoconstriction induced by exogenous substance P (5-25 micrograms/kg i.v.). We conclude that H3-receptors inhibit the release of transmitter from NANC nerves and that H3-receptors might play a role in regulation of neurogenic inflammatory responses in the airways.
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PMID:Histamine H3-receptors modulate nonadrenergic noncholinergic neural bronchoconstriction in guinea-pig in vivo. 248 90

The electrophysiological effects of histamine on neurons of the hypothalamic arcuate nucleus of the female rat were tested with extracellular single unit recordings in an in vitro slice preparation. Histamine increased the spontaneous neuronal firing rate in 63% of the arcuate cells tested. An inhibitory response to histamine was seen in only one of the 117 neurons tested. The excitatory response to histamine showed dose dependency and was stable during synaptic blockade (by high magnesium and low calcium concentrations) and across a temperature range of 29-37 degrees C. Administration of histaminergic type 1 (pyrilamine and chlorpheniramine) and type 2 (cimetidine) receptor blockers revealed that the excitatory responses to histamine were mediated by type 1 receptors. The same neurons were also tested for responses to norepinephrine, serotonin, acetylcholine and substance P. A significant correlation was found between responses to histamine and substance P: all units excited by substance P were also excited by histamine. This subclass of histamine-responsive arcuate neurons may play a role in the regulation of the anterior pituitary, since histamine and substance P have similar effects on LH and prolactin secretion.
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PMID:Histamine excites arcuate neurons in vitro through H1 receptors. 281 54

In spite of the research that has been performed, pruritus remains a poorly understood sensation. It is important to remember that the majority of information presented here is derived from observations of human subjects. One can only speculate as to how much of this information can be extrapolated to pruritus in animals. Pruritus is closely intertwined with pain and touch. Pain and pruritus sensations are carried on A delta and C fibers, ascend on the lateral spinothalamic tract, and terminate in various brain centers, including the thalamus and the cortex. The gate control theory of pain and pruritus describes the substantia gelatinosa cells as "swinging gates" to modify peripheral input and result in stimulation of higher centers. Central factors reduce or amplify the perception of these cutaneous sensations. Histamine is the classic mediator of pruritus, although it is still unknown whether a final common mediator of pruritus exists. Numerous other mediators include proteases, peptides, substance P, opiate peptides, prostaglandins, and leukotrienes. These may have pruritic properties directly, or may act as histamine liberators to cause pruritus.
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PMID:Pathophysiology of pruritus. 305 50

Utilizing 125I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated 125I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and 125I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of 125I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain. 369 67

The effects of pharmacological and nervous stimuli on the flow of secretion from the dog lateral nasal gland following catheterization are described. Drugs were injected close-arterially into the arterial supply to the nose, or intravenously. Cholinergic agonists (pilocarpine, methacholine), given intravenously (I.V.) or intra-arterially (I.A.), and stimulation of the vidian nerve produced a copious flow of secretion which was blocked by atropine. The adrenoceptor agonists phenylephrine (alpha) and salbutamol (beta 2), given I.V. or I.A., and stimulation of the vagosympathetic nerve produced a small but consistent flow of secretion. Histamine (50 micrograms), substance P (0.1 micrograms) and prostaglandin E1 (1-5 micrograms), injected I.A., produced small flows of secretion. Bradykinin (25 ng-50 micrograms), 5-hydroxytryptamine (100 ng-50 micrograms) and vasoactive intestinal peptide (VIP) (10 ng-50 micrograms) did not cause secretion. The total protein content, the composition of secretions as revealed by sodium dodecyl sulphate-polyacrylamide agarose gel electrophoresis, and changes in [Na] and [K] in relation to flow of secretion are described. Differences in ion and protein concentrations, and in protein composition, are described for vidian nerve-induced and vagosympathetically induced secretions. Electron microscopy revealed that the gland contains serous cells in the secretory region, and ducts morphologically similar to the intercalated, striated and excretory ducts of salivary glands.
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PMID:Lateral nasal gland secretion in the anaesthetized dog. 374 94

The responsiveness (grams per millimeter squared) and sensitivity (pD2 value) of various agonists were examined in isolated stored human bronchial and pulmonary arterial and venous preparations. In isolated bronchial muscles, large preparations (internal diameter about 6 mm) were less responsive (grams per millimeter squared) to contractile agents than smaller preparations (internal diameter approximately 2 mm). Noncumulative concentration-effect curves were produced in bronchial preparations using histamine, acetylcholine, carbachol and barium chloride. Histamine contracted both bronchial and vascular preparations whereas 5-hydroxytryptamine contracted only vascular tissues. The latter effect was always blocked by either methysergide or ketanserin. 5-hydroxytryptamine relaxed bronchial tissues that were contracted with either histamine, acetylcholine or prostaglandin E2. This relaxation was not antagonized by methysergide, ketanserin, propranolol or indomethacin. Dimaprit and 4-methyl histamine were without effect in isolated contracted bronchial preparations. Vasoactive intestinal peptide, Substance P and platelet-activating factor when added to preparations at resting tone failed to induce a contraction. These agents did not relax histamine-contracted isolated human pulmonary muscle preparations. Anti-immunoglobulin E antibody sometimes contracted isolated human bronchial muscle but not pulmonary vascular preparations. However, these data were difficult to assess because of the variations observed. Anti-immunoglobulin G antibody was inactive. Noradrenaline did not elicit a physiological response in isolated bronchial muscle preparations at concentrations which always induced a contraction in the pulmonary vascular preparations. In the presence of propranolol, noradrenaline neither contracted nor relaxed isolated human bronchial preparations. We also determined the sensitivity of isolated bronchial muscle preparations to isoproterenol, salbutamol and theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Response and sensitivity of isolated human pulmonary muscle preparations to pharmacological agents. 398 55

The actions of histamine on myenteric neurones were investigated with intracellular recording methods in guinea-pig small intestine. The actions of histamine at the ganglion cell soma were: membrane depolarization, increased input resistance, suppression of post-spike hyperpolarizing potentials, augmented excitability and repetitive spike discharge. Excitability was enhanced also at spike initiation sites remote from the cell body. Both H1, and H2, receptors were involved in the response to histamine. Dimaprit mimicked the responses to histamine in 80% and 2-methylhistamine in 50% of the trials. Cimetidine was an antagonist for histamine in 82% and for dimaprit in all of the trials. Pyrilamine blocked the actions of histamine in 59% of the cells and always blocked the action of 2-methylhistamine. Histamine mimicked slow synaptic excitation in the neurones, but was ruled out as a neurotransmitter for the slow excitatory post-synaptic potential (e.p.s.p.). Histamine either did not affect the responses to 5-hydroxytryptamine, substance P and acetylcholine or it potentiated the responses to these putative neurotransmitters for slow synaptic excitation. The results support the possibility that histamine released from mast cells by circulating peptidergic messengers, by neurotransmitters or during anaphylaxis could influence enteric nervous function.
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PMID:Intracellular study of effects of histamine on electrical behaviour of myenteric neurones in guinea-pig small intestine. 614 13


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