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)

Patients with essential hypertension (n = 45) had significantly lower substance P plasma levels (13.6 +/- 2.30 pg/ml) in comparison with a group of 24 normotensive subjects (45.4 +/- 7.18 pg/ml) analyzed by radioimmunoassay. Prazosin treatment for 2 weeks with 4.5 mg/day enhanced the substance P plasma level depending on its antihypertensive effect. Norepinephrine concentration in plasma was also elevated by prazosin. Dipeptidylpeptidase IV, dopamine-beta-hydroxylase and plasma renin activity were not changed significantly. The results indicate the participation of substance P in pathophysiological processes of human essential hypertension.
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PMID:Evidence of decreased plasma substance P levels in human essential hypertension and influence of prazosin treatment. 619 65

Norepinephrine, acetylcholine, and certain peptides are contained in mucosal nerves and have potent effects on transepithelial water and electrolyte fluxes. It is difficult to ascribe roles for these nerves as their sources are unknown. The present studies were undertaken to determine the origins of nerve fibers that are found in the mucosa of the guinea pig small intestine and which contain one of the following substances: vasoactive intestinal peptide, substance P, somatostatin, neuropeptide Y, cholecystokinin, or norepinephrine. Nerve fiber origins were ascertained by making lesions to sever pathways through which the nerves could reach the mucosa. The lesioning operations were homotopic autotransplants of short (2 cm) segments of intestine; myectomies, in which a 5-10-mm length of intestine was stripped of longitudinal muscle and myenteric plexus; and extrinsic denervation, in which nerves reaching the intestine through the mesentery were severed. The results of these studies, considered along with previously published work, led to the upcoming conclusions. Nerve fibers in the mucosa showing immunoreactivity for vasoactive intestinal peptide, somatostatin, cholecystokinin, and neuropeptide Y arise from cell bodies in the overlying submucous plexus. Substance P fibers arise in part from the overlying submucous plexus and in part from the overlying myenteric plexus. Mucosal norepinephrine fibers arise from extrinsic sympathetic ganglia. Enkephalin, gastrin-releasing peptide, and 5-hydroxytryptamine, which are in some enteric nerves, are not found in submucous nerve cells and few, if any, fibers containing these substances supply the mucosa. Thus, the mucosa receives a dense nerve supply, much of which arises locally from submucous ganglia.
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PMID:Origins of peptide and norepinephrine nerves in the mucosa of the guinea pig small intestine. 619 54

The role of the nerves in the hepato-duodenal ligament should be of special surgical interest, since these nerves are often injured in hepatic and biliary tract surgery. We have developed a microsurgical procedure for liver denervation. All visible nerves were resected after staining. Norepinephrine values in central liver tissue of denervated rats were only 18% of the corresponding values in innervated liver tissue, indicating an appreciable degree of sympathetic denervation. No detectable immunoreactivity of gastrin, cholecystokinin, vasoactive intestinal polypeptide, substance P, somatostatin or enkephalin were found within resected hepatic nerves. The described denervation procedure is simple and reproducible. It can be used to obtain additional information about the nervous regulation of various liver functions.
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PMID:A microsurgical method for denervation of the liver in the rat. 620 77

Capsaicin has been shown to specifically deplete substance P from primary sensory afferents, including sensory nerves innervating blood vessels of the cerebral circulation as well as other vascular beds. In order to further document the specificity of this treatment, we examined the effect of capsaicin treatment on 3 other types of nerves in the guinea pig. Four tissues were examined: cerebral arteries, the mesenteric artery, the heart and iris. Norepinephrine content was not altered after capsaicin treatment, confirming that adrenergic nerves are unaffected. As indices of cholinergic nerves, activities of choline acetyltransferase and acetylcholinesterase were also unchanged after capsaicin treatment. In addition, no significant differences in levels of vasoactive intestinal peptide in cerebral arteries and the heart were found in animals treated with capsaicin. These findings underscore the specificity of capsaicin treatment for substance P containing nerves.
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PMID:Specificity of capsaicin treatment in the cerebral vasculature. 647 98

1. Experiments were performed on barbiturate anaesthetized, spinalized cats to investigate the effect of microinjected noradrenaline or medetomidine on the release of immunoreactive substance P in the dorsal spinal cord following peripheral nerve stimulation. The presence of immunoreactive substance P was assessed with microprobes bearing C-terminus-directed antibodies to substance P. 2. Noradrenaline or medetomidine were microinjected into the grey matter of the spinal cord, near microprobe insertion sites, at depths of 2.5, 2.0, 1.5 and 1.0 mm below the spinal cord surface with volumes of approximately 0.125 microliters and a concentration of 10(-3) M. 3. In the untreated spinal cord, electrical stimulation of the ipsilateral tibial nerve (suprathreshold for C-fibres) elicited release of immunoreactive substance P which was centred in and around lamina II. Neither noradrenaline nor medetomidine administration in the manner described produced significant alterations in this pattern of nerve stimulus-evoked release. 4. In agreement with recent ultrastructural studies these results do not support a control of substance P release by catecholamines released from sites near to the central terminals of small diameter primary afferent fibres.
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PMID:Lack of effect of microinjection of noradrenaline or medetomidine on stimulus-evoked release of substance P in the spinal cord of the cat: a study with antibody microprobes. 752 62

Intracellular recordings were made in submucosal neurons from the guinea pig ileum to study the actions of norepinephrine and somatostatin on slow depolarizations induced by 2-chloroadenosine (CADO) and substance P. Local application (by pressure) of CADO and substance P induced a slow depolarization that occurred concomitantly with an increase in input membrane resistance. Norepinephrine, UK-14304 (alpha 2-adrenoceptor agonist), and somatostatin blocked the excitatory responses induced by CADO in a concentration-dependent manner. The alpha 2-adrenoceptor antagonists idazoxan and yohimbine antagonized these inhibitory effects of UK-14304 and norepinephrine. UK-14304 also decreased depolarizations induced by forskolin, but not those induced by the adenosine 3',5'-cyclic monophosphate analogue 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate. Slow depolarizations induced by substance P were blocked neither by UK-14304 nor by somatostatin. It was previously shown that staurosporine (an inhibitor of various protein kinases) and KT-5720 (an inhibitor of protein kinase A) inhibited slow depolarizations induced by CADO. Here, substance P depolarizations were inhibited by staurosporine and calphostin C (a blocker of protein kinase C) but not by KT-5720. In conclusion, activation of alpha 2-adrenoceptors and somatostatin receptors selectively blocks excitatory responses induced by CADO, most likely by inhibition of adenylyl cyclase and via pertussis toxin-sensitive G proteins. Slow depolarizations induced by substance P are independent of adenylyl cyclase activation and involve activation of protein kinase C.
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PMID:Interactions between inhibitory and excitatory modulatory signals in single submucosal neurons. 752 97

To determine whether a paravascular nerve projection or cross-innervation exists in the interscapular brown adipose tissue (BAT), the distribution of noradrenergic or peptidergic nerve fibers in intact or denervated interscapular BAT pads of mice was examined histochemically. Noradrenaline (NA) fibers were visualized by the glyoxylic acid condensation method, and neuropeptide Y (NPY) and substance P (SP) fibers were detected immunohistochemically. Numerous NA-positive fibers and a few NPY- or SP-positive fibers were observed around intralobular arterioles in intact BAT pads. Some NA-positive fibers and very few NPY- or SP-positive fibers were seen around interlobular arteries. NA- and NPY-positive fibers were also found around brown adipose cells in the parenchyme of BAT, whereas SP-positive fibers were absent around the cells. However, all sections cut from denervated BAT pads of unilaterally or bilaterally denervated animals showed a total absence of NA-, NPY- or SP-positive nerve fibers. Therefore, neither a paravascular projection of NA, NPY, and SP fibers to the BAT nor a cross-innervation of these nerve fibers between the left and right BAT pads exists in the mouse BAT.
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PMID:Absence of paravascular nerve projection and cross-innervation in interscapular brown adipose tissues of mice. 752 57

The possible control by monoamines of the spinal release of substance P- and calcitonin gene-related peptide-like materials (SPLM and CGRPLM, respectively) was investigated in vitro, using slices of the dorsal half of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Whereas the spontaneous outflow of SPLM and CGRPLM was changed by none of the agonists/antagonists of monoamine receptors tested, the overflow of both peptide-like materials due to 30 mM K+ was differentially affected by alpha 2-adrenoreceptor and dopamine D-1 receptor ligands. Noradrenaline (10 microM to 0.1 mM) and clonidine (0.1 mM) significantly reduced the K(+)-evoked overflow of SPLM, and both effects could be prevented by idazoxan (10 microM) and prazosin (10 microM) as expected from their mediation through the stimulation of alpha 2B-adrenoreceptors. In contrast, CGRPLM overflow remained unaffected by alpha 2-adrenoreceptor ligands. Dopamine D-1 receptor stimulation by SKF 82958 (10-100 nM) significantly increased the K(+)-evoked overflow of both SPLM and CGRPLM, and this effect could be prevented by the selective D-1 antagonist SCH 39166 (1 microM). Further studies with selective ligands of other monoamine receptors indicated that neither alpha 1- and beta-adrenergic receptors, dopamine D-2, nor serotonin 5-HT1A and 5-HT3 receptors are apparently involved in some control of the spinal release of CGRPLM and SPLM. These data are discussed in line with the postulated presynaptic control by monoamines of primary afferent fibres conveying nociceptive messages within the dorsal horn of the spinal cord.
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PMID:Monoaminergic control of the release of calcitonin gene-related peptide- and substance P-like materials from rat spinal cord slices. 768 7

The behavioural response to intraplantar injection of inflammatory mediators was examined using the rating scale developed to assess formalin-induced pain. Serotonin, bradykinin, prostaglandin E2, substance P and histamine induced dose-dependent favouring of the injected paw. Serotonin, bradykinin and prostaglandin E2 also induced transient dose-dependent paw elevation (lifting) and licking. Noradrenaline produced only a weak favouring response. Serotonin produced a synergistic increase in lifting and licking when combined with any of the other mediators, while all other combinations of agents taken two at a time showed additivity. There was apparent antagonism between some combinations in the favouring response; this may reflect overestimation of the baseline. The data indicate that (i) the overt spontaneous behaviour of rats can be used to evaluate spontaneous pain, (ii) the favouring response and the lifting and licking responses are qualitatively different, the former being similar to hyperalgesia and the latter possibility representing overt pain, (iii) hyperalgesia and overt pain are related, but the generation of overt pain involves specific mechanisms in addition to those required to induce hyperalgesia, and (iv) serotonin may function to enhance the pain-producing effects of inflammatory mediators, even when they lack intrinsic activity. The data show that some inflammatory mediators produce transient overt pain when high doses are injected into normal tissue in rats. Combination of inflammatory mediators with low doses of serotonin produced a synergistic increase in the pain response. The data suggest that serotonin released from platelets in injured tissue plays a central role in the pain associated with injury, and that serotonin antagonists may have promise as peripherally acting analgesics or analgesic adjuncts by blocking a synergistic process involved in algogenesis.
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PMID:Behavioural effects of intraplantar injection of inflammatory mediators in the rat. 789 81

The innervation and vasomotor responses to several vasoactive agents of guinea pig epicardial coronary veins were investigated by means of immunohistochemical, histochemical, ultrastructural and in vitro pharmacological techniques. The use of an antiserum to the general neuronal marker protein gene product 9.5 revealed that coronary veins are supplied by a network of fine varicose nerve fibres in the adventitia. The majority of the nerve fibres possessed neuropeptide Y (NPY) and tyrosine hydroxylase immunoreactivity. Only a few nerve fibres displayed substance P, neuropeptide K (NK) and calcitonin gene-related peptide (CGRP) immunoreactivity. In double stained preparations substance P immunoreactivity was co-localized with NK and CGRP in the same nerve fibres. Nerve fibres containing vasoactive intestinal peptide (VIP) immunoreactivity or acetylcholinesterase activity were not detected. Endothelin immunoreactivity was also found in the vein endothelial cells. Ultrastructural studies revealed the presence of axon varicosities at the adventitial-medial border. In vitro pharmacological studies showed that endothelin-1 and -2 elicited a significant contractile response of epicardial vein segments. Noradrenaline, NPY, serotonin and uridine 5'-triphosphate induced only a relatively weak contractile response in the vein segments. Although vasodilatory responses were difficult to examine in these preparations, it was found that substance P, CGRP and VIP elicited a relaxation of the vein segments. These results indicate that guinea pig epicardial coronary veins are innervated by several nerve populations, however, the control of vasomotor tone of coronary veins appears to be predominantly regulated by 'non-neuronal' vasoactive agents such as endothelin and 5-HT.
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PMID:The innervation of guinea pig epicardial coronary veins: immunohistochemistry, ultrastructure and vasomotility. 791 47


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