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 study aims to establish the nature of the chemical mediator which produces the IP (presynaptic inhibition) of the mechanoreceptive afferents reaching the NTS (nucleus tractus solitarius) of the frog. To this end we have examined the effects of the administration of SP (substance P) and of one of its antagonists in the IV ventricle, in both normal and unilaterally axotomized preparations at the level of the glossopharyngeal nerve. In particular we have examined the size of the afferent discharge of the glossopharyngeal-hypoglossus reflex arc and the PAD (primary afferent depolarization) phenomena recorded from the dorsal root of the XII. While in normal preparations the SP reduces the size of the reflex discharge, on the contrary the antagonist increases it; the electrical activity of PAD appears to be enhanced by SP and reduced by the antagonist. Lastly SP normalises the enhanced response produced by axotomy. All the observed effects favour the hypothesis that the IP, which appears in the NTS with the activation of the mechanoreceptive afferents, is brought about by the release of S.P. from their central endings.
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PMID:[Action of substance P and one of its synthetic antagonists on the nucleus tractus solitarius]. 247 69

In canine and porcine coronary arteries, experimental atherosclerosis (induced by endothelial denudation followed by a high-cholesterol diet) potentiates the vasoconstrictor effects of histamine, serotonin, and ergonovine. In isolated human atherosclerotic coronary arteries, only hypersensitivity to histamine has been demonstrated. This discrepancy could be due to several factors. First, the atherosclerotic lesions in human vessels are different from those observed in the animal, since experimental atherosclerosis often corresponds only to the early stage of the disease in humans. Second, the human atherosclerotic coronary arteries were isolated mainly from patients with cardiac failure, a condition that alters the responses of coronary smooth muscle to vasoactive amines. With regard to endothelium-dependent vasodilators, marked attenuations of the relaxations to substance P, bradykinin, and the Ca2+ ionophore A23187 have been described in isolated human atherosclerotic arteries. Acetylcholine elicits variable responses in these preparations and even if the arteries are devoid of atherosclerotic lesions, it often fails to relax them. In addition to this endothelial dysfunction, severely atherosclerotic human coronary vessels exhibit a slightly decreased responsiveness to nitroglycerin and SIN-1 but not to forskolin. Another abnormality of the smooth muscle is a marked attenuated beta-adrenergic relaxation. Thus, atherosclerosis of human coronary vessels induces not only marked alterations in endothelium-dependent responses but also modifies the sensitivity to several endothelium-independent vasodilators.
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PMID:Atherosclerosis and responses of human isolated coronary arteries to endothelium-dependent and -independent vasodilators. 248 97

1 The inhibitory action of manoalide on vascular relaxation was characterized. Manoalide was a potent inhibitor of endothelium-dependent relaxations in the isolated aorta of the rabbit. Responses to acetylcholine (ACh), A23187 and substance P were reduced by manoalide in a dose-dependent manner whilst those to nitroglycerin were unaffected. 2 Repeated washing of manoalide-treated tissues did not restore the relaxant response to ACh, indicating an irreversible action of manoalide. Scanning electron microscopic studies revealed that the endothelium remained intact on manoalide-treated tissues. 3 Rabbit aortae from which the endothelium had been removed relaxed in response to perfusion with ACh when delivered via an upstream endothelium-bearing tissue, indicating release of an endothelium-derived relaxant factor (EDRF). Incubation of the tissue without endothelium with manoalide (100 nM; 30 min) or inclusion of manoalide in the superfusate at a point just distal to the endothelium bearing tissue did not reduce the relaxant potency of EDRF. 4 Contractile responses of the guinea-pig isolated ileum to ACh were not affected by manoalide and, furthermore, binding of [3H]-quinuclidinyl benzilate to striatal membranes was not reduced by manoalide except at very high concentrations. 5 Manoalide therefore appears to inhibit vascular relaxation with a selectivity directed towards that mediated by EDRF. A direct antagonism of neither cholinoceptors nor EDRF receptors occurs and it is suggested that manoalide acts at a site within the endothelium to inhibit the synthesis and/or release of EDRF. Based upon these and previous data the possibility that EDRF is lipid-like or controlled by an arachidonic acid metabolite must continue to be considered.
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PMID:The inhibition of release of endothelium-derived relaxant factor by manoalide, a potent inhibitor of phospholipase A2. 282 28

The roles of putative central neurotransmitters in the control of blood pressure have been reviewed with respect to the cardiovascular functions of individual nerve pathways in the medulla oblongata and spinal cord. Vasomotor activity of sympathetic preganglionic neurones originates from spinally-projecting neurones in the ventrolateral medulla which may include adrenaline neurones of the C1 group and serotonin neurones in the lateral B1 and B3 groups. Other bulbospinal monoamine nerves may modulate vasomotor activity at the spinal level, but the mechanism of this modulation is controversial. Evidence for two descending sympatho-inhibitory pathways has emerged: a noradrenergic projection from the A5 cell group and a serotonergic projection from the medullary raphe (medial B1 and B2 groups). The vasomotor influence of other bulbospinal pathways is unclear. Baroreflex control of blood pressure is mediated through the solitary tract nucleus (NTS). L-Glutamate and substance P are considered as candidates for transmitters in baroreceptor afferents to the NTS. Transmitters in efferent nerves relaying baroreflex activity from the NTS to cardiovagal motoneurones, medullary vasomotor neurones or sympathetic preganglionic neurones have not been identified but the monoamine transmitters present in the NTS appear to modulate baroreflexes. Noradrenaline and serotonin nerve endings may facilitate the vasodepressor component of the baroreflex while adrenaline nerves possibly inhibit the cardiovagal mechanism. Enkephalins and vasopressin act in the NTS to raise blood pressure and nerves containing these neuropeptides may constitute important links in reciprocal cardiovascular pathways between the lower brainstem and hypothalamus.
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PMID:Blood pressure control by neurotransmitters in the medulla oblongata and spinal cord. 286 Jan 49

In vivo experiments were performed in autoperfused hindlimbs of rabbits to investigate the role of endothelium-mediated vasomotion in resistance-sized vessels. The flow responses to the vasodilators acetylcholine (ACh), ATP, and substance P (SP), all of which have been shown to act in an endothelium-dependent manner in large conduit arteries, were studied before and after exposure of the hindleg vasculature to gossypol (a potent inhibitor of endothelium-mediated vasodilation in vitro). The flow responses to adenosine (ADO), nitroglycerin (GTN), and prostaglandin E2 (PGE2), which induce relaxation by a direct effect on vascular smooth muscle, were tested in the same manner. All vasodilators induced dose-dependent increases in femoral flow up to two- to threefold when administered intra-arterially. After gossypol, the flow responses to the endothelium-dependent compounds (ACh, ATP, and SP) were severely reduced (by 88 +/- 3%, P less than 0.01) or sometimes were converted to constrictions (ATP). The flow increases induced by ADO, PGE2, and GTN remained largely unaffected. Sham treatment (gossypol solute only), exposure to indomethacin (10 microM), and ganglionic blockade had no differential effect on the flow responses. The selective action of gossypol in suppressing the flow responses to the endothelium-dependent compounds ACh, ATP, and SP is consistent with a vasomotor role for endothelial cells in resistance-sized vessels in vivo.
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PMID:Selective inhibition of endothelium-dependent dilation in resistance-sized vessels in vivo. 288 20

By using a multibarrelled microelectrode, the possibility that putative transmitters may influence on the field potential evoked in the solitary tract nucleus by electrical stimulation of the carotid sinus nerve (the NTS response) was examined electrophysiologically in the cat. After iontophoretic application of a selective antagonist to the putative transmitter, it was determined whether or not the NTS response was influenced. Both substance P antagonist and naloxone altered the NTS response recorded in the depressor and apneic (or hypopneic) response zone as well as in the pressor and apneustic (or inspiratory) response zone throughout the rostral, intermediate and commissure regions, suggesting that substance P and opioid peptide may play the role of excitatory transmitters. Under the polarizing cathodal current which may activate inhibitory inputs to the site of the NTS response, bicuculline and prazosin strongly enhanced the NTS response recorded in the pressor and apneustic zone, while naloxone weakly enhanced the NTS response recorded in the depressor and apneic zone. These results suggest that gamma-aminobutyric acid, alpha-adrenergic agonist and opioid peptide may have an inhibitory influence on the NTS response.
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PMID:Study of possible transmitters in the solitary tract nucleus of the cat involved in the carotid sinus baro- and chemoreceptor reflex. 288 9

We have reported that microinjection of angiotensin II (ANG II) into the nucleus tractus solitarius of urethan-anesthetized normotensive rats produces an increase in mean arterial pressure (MAP) over the dose range 50-500 pmol. The effect in spontaneously hypertensive rats (SHR) is now reported. Over the range 100-500 pmol SHR exhibit increases in MAP and heart rate greater than Wistar-Kyoto or Sprague-Dawley rats. SHR did not exhibit exaggerated responses to intravenous phenylephrine, suggesting a central site of increased responsiveness to ANG II. We also found depressor effects in Sprague-Dawley at lower doses (0.1 and 1 pmol). The decreases in MAP were extremely variable and not dose related. A selected dose of additional neuropeptides identified in the NTS was tested. Somatostatin, bradykinin, and vasoactive intestinal peptide (0.5 nmol) were without cardiovascular effects. Oxytocin and vasopressin, however, produced significant increases in MAP. Substance P produced a very small but significant increase in heart rate and MAP. Interaction between the vasopressin and ANG II pressor effects was studied, and each proved to be independent.
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PMID:Neuropeptide action in nucleus tractus solitarius: angiotensin specificity and hypertensive rats. 293 Oct 31

Golgi-impregnated and methionine-enkephalin (ME)- and substance P (SP)-immunoreactive neurons were studied throughout the feline nucleus tractus solitarii. The majority of Golgi-impregnated neurons in the NTS range in size from 5 to 18 micron. A noticeable exception is the large (15-30 micron) neurons of the ventrolateral subdivision. The Golgi-impregnated neurons possess dendritic trees which remain within the nucleus and even at times within the particular subdivisions. Golgi-impregnated neurons had a variety of spine forms: pedunculated, sessile, filiform, and complex. A number of neurons exhibited axons originating from the cell and they could be followed for distances up to 100 micron. ME- and SP-immunoreactive neurons were found in commissural, medial, lateral, and parvocellular subdivisions while ME-immunoreactive neurons were situated additionally in the intermediate and ventrolateral subdivisions. Both types of immunostained neurons were similar in size (6-20 micron) and shape of dendritic arbor. One population of ME-immunoreactive neurons resembled the large ventrolateral neurons of the Golgi impregnations. Neither type of immunostained neuron possessed the extensive dendritic arbor, numbers of spines, or axons of the Golgi-impregnated neurons. The presence of ME- and SP-immunoreactive neurons in regions which are associated with autonomic regulation suggests that these two peptides are involved in this process.
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PMID:The nucleus tractus solitarii of the cat: a comparison of Golgi impregnated neurons with methionine-enkephalin- and substance P-immunoreactive neurons. 619 50

The immunocytochemical localizations of substance P, neurotensin, enkephalin and the catecholamine-synthesizing enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase were examined in the rat parabrachial region. The immunoreactivity for each marker was compared with the distribution of superimposed autoradiographic labeling of parabrachial afferents after unilateral injection of 3H-amino acids into the caudal portion of the medial nucleus of the solitary tract (m-NTS). Substance-P- and neurotensinlike immunoreactivity (SPLI and NTLI, respectively) were localized primarily in varicose processes in the ventrolateral quadrant of the parabrachial region. The SPLI and NTLI were differentially localized with respect to each other; however, both peptides were detected in regions of the parabrachial containing dense autoradiographic label. In contrast, enkephalinlike immunoreactivity (ELI), tyrosine hydroxylase, and dopamine-beta-hydroxylase were detected in processes and a few perikarya located outside the ventrolateral parabrachial region. The ELI was primarily in the dorsolateral, and the catecholamine-synthesizing enzymes were primarily in the medial parabrachial regions which contained sparse autoradiographic labeling of transported amino acids. We conclude that in the rat parabrachial region, SPLI and NTLI are contained within two distinct populations of afferents which may originate from perikarya in the caudal m-NTS, whereas ELI and the catecholamines are more likely to be found in other afferents or possibly in intrinsic neurons.
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PMID:Substance P, neurotensin, enkephalin, and catecholamine-synthesizing enzymes: light microscopic localizations compared with autoradiographic label in solitary efferents to the rat parabrachial region. 620 25

To determine the role that vasoactive neuropeptides, calcitonin gene-related peptide, and substance P play in tissue-blood flow regulation during early septic shock, we examined the responsiveness of arteries removed from pigs 3 h after administration of Escherichia coli lipopolysaccharide or saline vehicle. The carotid, cranial mesenteric, and left anterior descending coronary arteries were excised, and rings were cut from each vessel. Constrictor responses were obtained to cumulative doses of norepinephrine or potassium chloride. Rings were reconstricted and challenged with acetylcholine, substance P, calcitonin gene-related peptide, and nitroglycerin. Lipopolysaccharide significantly increased the cranial mesenteric artery's response to high concentrations of norepinephrine and the response to nitroglycerin in all vessels. This enhancement of responses to nitroglycerin suggests augmented smooth-muscle responsiveness to an exogenous source of nitric oxide, possibly associated with early depression of basal endothelial function. Depression of agonist-induced nitric oxide release may mask such enhancement with endothelial-dependent dilators and may enhance the response to adrenergic constrictors in some vascular beds.
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PMID:Early endotoxic shock results in enhanced vasodilator responses to nitroglycerin but unaltered responses to neuropeptides calcitonin gene-related peptide and substance P. 753 18


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