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)

In atrial preparations obtained from reserpine-pre-treated guinea-pigs, incubated in the presence of 1 microM atropine plus 1 microM CGP 20712A (a beta 1 blocking drug), a positive inotropic effect due to CGRP release from capsaicin-sensitive sensory neurons was induced by electrical field stimulation (EFS). This response was concentration-dependently reduced by noradrenaline (0.01-3 microM), neuropeptide Y (NPY, 3-300 nM) and adenosine triphosphate (ATP, 1-30 microM). On the other hand, the overflow of [3H]-noradrenaline from sympathetic nerve terminals induced by EFS in isolated atria obtained from normal untreated animals was not modified in 10 nM calcitonin gene-related peptide (CGRP). Substance P (SP) and neurokinin A (NKA), at concentrations ranging from 0.01 to 1 microM did not affect the cardiac response to field stimulation of adrenergic terminals of atrial tissue. These findings demonstrate that all the co-transmitters stored in adrenergic nerve terminals have a modulatory role on the efferent function of cardiac capsaicin-sensitive sensory neurons, while cardiac adrenergic neurotransmission is not influenced by the peptidergic transmitters released from sensory neurons.
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PMID:Modulation by adrenergic transmitters of the efferent function of capsaicin-sensitive nerves in cardiac tissue. 172 21

The effect of acrylamide intoxication on the innervation and local control of the rabbit central ear artery was investigated. There was no difference in the noradrenaline, neuropeptide Y and calcitonin gene-related peptide tissue content between control and experimental animals. There was, however, a slight reduction in catecholamine histofluorescence. Although the contractile efficiency of the rabbit central ear artery as measured by responses to potassium chloride was unchanged, nerve-mediated contractile responses were significantly attenuated in acrylamide-treated animals. Contractile responses induced by exogenous alpha,beta-methylene ATP were markedly increased after acrylamide treatment, in contrast to contractions induced by exogenous noradrenaline which were attenuated at maximal concentrations. Modulatory effects of nerve-mediated contractile responses by neuropeptide Y were unaffected by acrylamide intoxication. It therefore appears that acrylamide intoxication damages sympathetic cotransmission, perhaps with preferential action on the purinergic component. Endothelium-dependent relaxant responses to acetylcholine and substance P were attenuated in acrylamide-treated animals, whereas relaxant responses mediated by calcitonin gene-related peptide (endothelium independent) were unaffected. The question of whether the damage to the endothelial cell action is a primary effect, or a secondary consequence of sympathetic nerve damage, is discussed.
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PMID:Changes in sympathetic and endothelium-mediated responses in the rabbit central ear artery after acrylamide treatment. 175 64

The modulation of Ca2+ currents by neurotransmitters was studied in freshly dissociated rat spinal cord neurons, using the whole-cell patch-clamp technique. GABA, baclofen, adenosine, ATP, serotonin, norepinephrine, somatostatin, and dynorphin A inhibited the current through Ca2+ channels in a substantial fraction of cells, while substance P, vasoactive intestinal polypeptide, [D-ala2,d-leu5]-enkephalin, cholecystokinin-8 (sulfated), calcitonin gene-related peptide, angiotensin II, neurotensin, vasopressin, and thyrotropin-releasing hormone had no effect. In the case of baclofen, the inhibition is mediated, at least in part, by a GTP-binding protein. Suppression of Ca2+ current by neurotransmitters may represent a mechanism of presynaptic inhibition in the spinal cord.
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PMID:Neurotransmitter modulation of calcium current in rat spinal cord neurons. 196 36

In addition to the classical transmitters noradrenaline and acetylcholine, other transmitters have been identified in perivascular nerves, including 5-hydroxytryptamine, ATP and a number of peptides. This paper discusses pre- and postjunctional neuromodulation of vascular transmission, and cotransmission involving noradrenaline, ATP and neuropeptide Y in sympathetic nerves, acetylcholine and vasoactive intestinal polypeptide in parasympathetic nerves, and substance P, calcitonin gene-related peptide and ATP in 'sensory-motor' nerves. Vasomotor nerves derived from intrinsic neurones, for example in the heart and gut, are also discussed. Subpopulations of endothelial cells store and release a variety of substances, including acetylcholine, substance P, ATP, 5-hydroxytryptamine, vasopressin and angiotensin II, that act on receptors on endothelial cells and lead to the production of endothelium-derived relaxing factor (identified as nitric oxide) which, in turn, produces vasodilation in response to changes in flow and hypoxia. Endothelium-derived contracting factors such as endothelin may also be released. There appears to be a resting dynamic balance between endothelium-derived vasodilator tone and sympathetic vasoconstrictor tone, which is altered under different physiological and pathophysiological circumstances. Long-term (trophic) interactions between perivascular nerves and endothelial cells are discussed, as are the changes in vascular control mechanisms that occur with ageing and hypertension and in the nerves that remain following trauma or surgery.
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PMID:Local mechanisms of blood flow control by perivascular nerves and endothelium. 198 71

The effect of a potassium channel activator, cromakalim (BRL 34915), on excitatory nonadrenergic noncholinergic (e-NANC) and cholinergic neural bronchoconstriction was studied in guinea pigs. We monitored airway opening pressure as an index of airway caliber. After atropine (1 mg/kg iv.) and propranolol (1 mg/kg iv.), bilateral vagal stimulation evoked an e-NANC response. Cromakalim did not alter basal airway caliber, but reduced the e-NANC response to vagal stimulation in a dose-dependent manner, with a maximal inhibition of 71.9 +/- 9.2% (mean +/- S.E.) at 400 micrograms/kg i.v. (P less than .01). Pretreatment with phentolamine (2.5 mg/kg i.v.) had no effect on the inhibitory response produced by cromakalim but glibenclamide (25 mg/kg iv.), an inhibitor of ATP-sensitive potassium channels, blocked its effect. Cromakalim had no inhibitory effect on exogenous substance P (5-25 micrograms/kg i.v.)-induced bronchoconstriction. In animals depleted of tachykinins by capsaicin (50 mg/kg s.c.) pretreatment, cromakalim had an inhibitory effect on both vagalcholinergic and exogenous acetylcholine (0.3-2 micrograms/kg i.v.)-induced bronchoconstriction, although the inhibitory effect was significantly greater on neural stimulation. We conclude that potassium channels modulate both e-NANC and cholinergic neurotransmission, and to a lesser extent acetylcholine-induced bronchoconstriction in guinea pig airways.
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PMID:A potassium channel activator modulates both excitatory noncholinergic and cholinergic neurotransmission in guinea pig airways. 210 38

Potassium (K+) channels are present on airway smooth muscle cells, and their activation results in hyperpolarization and relaxation. Because these effects may have therapeutic relevance to asthma, we examined the activity of the active L-enantiomer of cromakalim, BRL 38227 (lemakalim), a selective K+ channel activator, against a variety of spasmogens in human bronchi in vitro. BRL 38227 produced relaxation of bronchi with either resting tone or tone induced by histamine, carbachol, neurokinin A, or KCl (20 mM) with an efficacy (%Emax) of 60 to 80% of that of isoproterenol and an EC50 (the concentration producing 50% of the maximal response) of 0.2 to 0.6 microM. However, BRL 38227 had a significantly lower potency and efficacy against 80 mM KCl than against the other spasmogens (%Emax, 12% of isoproterenol and EC50, 7.2 microM; p less than 0.005 and p less than 0.001, respectively), supporting the view that BRL 38227 acts on K+ channels. The D-enantiomer BRL 38226 was less potent (EC50, 2.6 microM) than BRL 38227 and produced only 43% of the isoproterenol relaxation. BRL 38227-induced relaxation was significantly inhibited by the ATP-sensitive K+ channel antagonist glibenclamide (0.1 and 1 microM), with a three-fold and eight-fold shift to the right of the dose-response curve, respectively. In the presence of a maximal relaxation induced by the calcium voltage-dependent channel antagonist verapamil, BRL 38227 was able to produce an additional 37% relaxation response. Thus, BRL 38227 is an effective relaxant of human airway smooth muscle, and this activity results from an action at K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The action of a potassium channel activator, BRL 38227 (lemakalim), on human airway smooth muscle. 212 15

The recent discoveries of vascular neuroeffector control mechanisms, involving a wide variety of neurohumoral agents, pre- and postjunctional neuromodulation, and cotransmission, leave the field poised for growth in new directions. Some of these are outlined in this article, including: the development of methods for quantitation of the pattern and density of different types of perivascular nerves; exploration of the potent actions of purine nucleotides and nucleosides on vascular smooth muscle and/or endothelial cells, particularly in relation to the development of drugs of therapeutic potential; expansion of studies of the regulatory implications of cotransmitter release of ATP together with noradrenaline from some sympathetic perivascular nerves and of VIP together with acetylcholine from some parasympathetic nerves; autoradiographic localization of receptors for monoamines, peptides of and purines in blood vessels; wider studies of "axon reflex" control of the circulation and of the roles of substance P; investigation of development, aging, and regeneration of different perivascular nerve types, and the long-term "trophic" actions of some neurohumoral agents. Lastly, the time is ripe to study abnormalities in neurohumoral control of vessels in disease and after chronic exposure to drugs.
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PMID:Neurohumoral control of blood vessels: some future directions. 240 87

ATP and substance P were examined as possible mediators of non-adrenergic, non-cholinergic excitatory transmission in chicken rectum. ATP and the non-degradable ATP analogue, alpha, beta-methylene ATP, mimicked the response to nerve stimulation. Substance P either produced a maintained contraction after a long latency or was inactive. After desensitization of the P2-purinoceptor by alpha, beta-methylene ATP, the responses to ATP and nerve stimulation were abolished, while the response to carbachol was little affected. It is concluded that ATP may be the transmitter in non-adrenergic, non-cholinergic excitatory nerves supplying the chicken rectum.
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PMID:Investigations into the identity of the non-adrenergic, non-cholinergic excitatory transmitter in the smooth muscle of chicken rectum. 241 Jan 83

In the guinea-pig bladder, contractile responses to substance P (0.3 microM) and VIP (3 microM) were unaffected by P2-purinoceptor desensitization with alpha,beta-methylene ATP (3 X 10(-6) M), while the responses to stimulation of the non-cholinergic excitatory nerves (4-16 Hz) were abolished. The evidence presented suggests that ATP or a related purine nucleotide, and not VIP or substance P, is responsible for the non-cholinergic excitatory component of the nerve-mediated response.
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PMID:Evidence against VIP or substance P being the transmitter in non-cholinergic excitatory nerves supplying the guinea-pig bladder. 241 May 87

Human lung bronchiolar segments (about 2 mm long and with a diameter of 0.6-1.5 mm) were dissected and circular muscle tension recorded. Airways were identified by histology and in some preparations by relaxant responses to noradrenaline (0.1-10 microM). Adenosine (1-100 microM) produced only very weak contractions, whereas carbachol (EC50 = 0.40 microM), histamine (EC50 = 0.63 microM), prostaglandin D2 (EC50 = 0.50 microM), substance P (EC50 = 4.6 microM) and ATP (1-100 microM) produced much greater ones. The contractions generally developed rapidly and were stable. The mean maximum increase in tension achieved with the most efficient constrictor, carbachol, was 0.5 g. ATP was the least efficient producing only about 40% of carbachol's maximum. Terbutaline, theophylline and enprofylline relaxed carbachol (2.0 microM = EC70)-contracted preparations. Terbutaline (3-3000 nM) relaxed 4 out of 11 bronchioles. Theophylline (10-4000 microM) and enprofylline (1-400 microM) consistently relaxed the bronchiolar preparations including those exhibiting little responsiveness to the beta 2-adrenoceptor agonist. Since enprofylline (which does not block adenosine receptors) was a five times more potent relaxant than theophylline and since adenosine produced only weak contractions, antagonism of adenosine receptors is probably not involved in relaxation of the small airways. It is suggested that the present data, which apparently differ from those obtained with lung parenchymal strips, are of relevance for human small airways responsiveness.
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PMID:Effects of bronchoconstrictors and bronchodilators on a novel human small airway preparation. 241 19


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