Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Local mechanisms of blood flow control by perivascular nerves and endothelium. 198 71

In order to determine which neurotransmitters and neuropeptides are utilized by the neurons of the mesencephalic trigeminal nucleus and by the fibres making synaptic contact with these primary sensory cells, we have set up an immunohistochemical study using antibodies against 17 major neurotransmitters and neuropeptides in the rat. Apart from some intracellular immunostaining for glutamate, no immunoreactivity to any of the tested neurotransmitters and neuropeptides could be detected inside mesencephalic nucleus of the trigeminal nerve neurons. Our immunohistochemical observations indicate that mesencephalic nucleus of the trigeminal nerve neurons receive input from various nerve fibres that appear to utilize serotonin, GABA, dopamine, noradrenaline (and likely glutamate) as transmitters. The innervation appeared randomly distributed over all mesencephalic nucleus of the trigeminal nerve neurons. The presence of substance P, cholecystokinin, vasoactive intestinal polypeptide, bombesin/gastrin releasing peptide, [Leu]enkephalin and neuropeptide Y observed in some fibres that contact with mesencephalic nucleus of the trigeminal nerve neurons, presumably reflect the co-existence of these peptides with one of the neurotransmitters.
 ...
PMID:Neurotransmitters and neuropeptides within the mesencephalic trigeminal nucleus of the rat: an immunohistochemical analysis. 198 70

A newly identified myopathy of the internal anal sphincter is described. In the affected family, at least one member from each of five generations had severe proctalgia fugax; onset was usually in the third to fifth decades of life. Three members of the family have been studied in detail. Each had severe pain intermittently during the day and hourly during the night. Constipation was an associated symptom, in particular difficulty with rectal evacuation. Clinically the internal anal sphincter was thickened and of decreased compliance. The maximum anal canal pressure was usually increased with marked ultraslow wave activity. Anal endosonography confirmed a grossly thickened internal anal sphincter. Two patients were treated by internal anal sphincter strip myectomy; one showed marked improvement and one was relieved of the constipation but had only slight improvement of the pain. The hypertrophied muscle in two of the patients showed unique myopathic changes, consisting of vacuolar changes with periodic acid-Schiff-positive polyglycosan bodies in the smooth muscle fibers and increased endomysial fibrosis. In vitro organ-bath studies showed insensitivity of the muscle to noradrenaline, isoprenaline, carbachol, dimethylpiperazinium, and electrical-field stimulation. Immunohistochemical studies for substance P, calcitonin gene-related peptide, galanin, neuropeptide Y, and vasoactive intestinal peptide showed staining in a similar distribution to that in control tissue. A specific autosomal-dominant inherited myopathy of the internal anal sphincter that causes anal pain and constipation has been identified and characterized.
 ...
PMID:Hereditary internal anal sphincter myopathy causing proctalgia fugax and constipation. A newly identified condition. 199 4

The effect of short-term and long-term streptozotocin-induced diabetes on the pattern of distribution and tissue content of adrenergic and peptidergic nerves in ileum and distal (descending) colon of the rat was examined using immunohistochemical, biochemical, and immunochemical techniques. The effect of short-term streptozotocin-induced diabetes on the level of noradrenaline compared with weight-restricted (starved) and untreated controls in the celiac (celiac-superior mesenteric ganglia complex) and inferior mesenteric ganglia, which supply the two regions of the intestine, was also compared. The pattern of change in the distribution of dopamine-beta-hydroxylase-, substance P-, calcitonin gene-related peptide-, and vasoactive intestinal polypeptide-like immunoreactive nerve fibres that was observed in the ileum from diabetic rats was not evident in the myenteric plexus of distal colon. In contrast to the ileum, there was no evidence of degenerative change in any of the nerve types investigated in the myenteric plexus of the distal colon. The level of vasoactive intestinal polypeptide in the diabetic rat ileum was significantly increased, whereas the level of noradrenaline was reduced; no such changes were observed in the distal colon. The tissue content of noradrenaline in the celiac ganglion, which projects to the ileum, was increased at 8-week diabetes compared with both weight-restricted and untreated controls, whereas the diabetic state had no effect on the levels of noradrenaline of the inferior mesenteric ganglion, which projects to the distal colon. It is concluded that there is a differential effect of streptozotocin-diabetes on different regions of the rat intestine. The adrenergic and peptidergic innervation of the distal colon were changed little compared with ileum. This may be explainable in terms of the different functional roles of these two regions of the intestine and/or by the difference in origin of the sympathetic nerves supplying the two regions of the intestine.
 ...
PMID:Differential effect of streptozotocin-induced diabetes on the innervation of the ileum and distal colon. 200 99

The nasal and tracheobronchial circulations are both innervated by parasympathetic cholinergic, sympathetic adrenergic, and sensory neurones. All three systems contain neuropeptides. Structurally the systems are similar, with subepithelial networks and deeper networks of sinuses or sinusoids. The nose in addition has arteriovenous anastomoses, not described for the tracheobronchial tree. Parasympathetic nerves release acetylcholine and vasoactive intestinal polypeptide, both dilators; sympathetic nerves release noradrenaline and neuropeptide Y, both constrictors; and the sensory nerves release substance P, neurokinin A and calcitonin gene-related peptide, all dilators. The last are important in axon reflexes. Many inflammatory mediators also act on both vascular beds in response to tissue inflammation or damage. Both vascular beds are under reflex control, probably acting mainly via the sympathetic system. In particular, peripheral chemoreceptors cause vasoconstrictions in the nose and trachea, and pulmonary C-fibre receptors and cardiac receptors cause vasodilations in the nose and lower airways. Reflexes from carotid sinus baroreceptors and slowly adapting pulmonary stretch receptors seem to be inactive on the nasal and tracheal vascular beds.
 ...
PMID:Comparison between the vascular beds of upper and lower airways. 207 50

In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP-LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system.
 ...
PMID:Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres. 210 40

Changes in the innervation of the cardiovascular system, urinogenital tract and sympathetic and non-sympathetic ganglia have been examined following long-term sympathectomy. Patterns of innervation were investigated using histochemical and immunohistochemical techniques, while levels of noradrenaline and neuropeptides were measured by neurochemical assays. Large doses of guanethidine (50 mg/kg) were given daily for 3 weeks to 8-day-old rat pups, which were killed at 6 or 20 weeks of age. In both age groups noradrenergic nerves were severely depleted or absent, while in some regions dramatic increases of calcitonin gene-related peptide levels were demonstrated. This was revealed by an increase in the density of nerve fibres and in calcitonin gene-related peptide content (up to 18-fold), most notably in the right atrium and superior cervical ganglion. No changes in substance P- or vasoactive intestinal polypeptide-immunolabelled nerves were seen. Conversely, short-term sympathectomy by 6-hydroxy-dopamine treatment caused a depletion of noradrenaline which was not accompanied by an increase in the number or content of calcitonin gene-related peptide-immunolabelled nerves. The possibility that nerve growth factor is involved in the mechanism of hyperinnervation by calcitonin gene-related peptide-containing sensory nerves following long-term sympathectomy is discussed.
 ...
PMID:Marked increases in calcitonin gene-related peptide-containing nerves in the developing rat following long-term sympathectomy with guanethidine. 211 38

1. We have compared the ability of various tachykinins and selective tachykinin receptor agonists to induce contraction of the endothelium-denuded rabbit pulmonary artery (RPA) and hamster trachea (HT) and have estimated the affinity of some newly developed NK2 selective antagonists in the same tissues. 2. In confirmation of previous findings, experiments with the agonists indicated that NK2 receptors are the main if not the sole mediators of the response to tachykinins in both RPA and HT. No evidence for significant degradation of neurokinin A (NKA) was found in either tissue when experiments were repeated in the presence of a mixture of peptidase inhibitors (thiorphan, captopril and bestatin, 1 microM each). 3. The peptide antagonists tested were: Peptide I = [Tyr5, D-Trp6,8,9, Arg10]-NKA(4-10); Peptide II = [Tyr5, D-Trp6,8,9, Arg10]-NKA(3-10); Peptide III = Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2. The three peptides produced a concentration-dependent rightward shift of the concentration-response curve to NKA in both RPA and HT with no significant depression of the maximal response attainable. The slopes of the Schild plots were not significantly different from unity, indicating a competitive antagonism. Peptides I and II were about 100 times more potent in the RPA than in the HT, while Peptide III was about 100 times more potent in the HT than RPA. 4. The pA2 values obtained in these two tissues with the three antagonists were not significantly different when tested in the absence or presence of peptidase inhibitors, or when a selective NK2 receptor agonist, [beta Ala8]-NKA(4-10) was used instead of NKA. Similar pA2 values were obtained after 15 or 90min of incubation with the antagonists. Peptides I, II and III had no inhibitory effect on contractions produced by noradrenaline in the RPA or by carbachol in the HT. 5. Peptides I, II and III showed weak or no antagonistic activity toward the vasodilatator effect of substance P in the dog carotid artery (NK, receptor-mediated) or toward the contractile effect of neurokinin B in the rat portal vein (NK3 receptor-mediated). 6. These results provide pharmacological evidence for heterogeneity of NK2 receptors in the RPA and HT. The NK2 receptors present in these tissues are not discriminated by natural tachykinins or selective agonists, but are recognized with very different affinity by NK2 receptor antagonists.
 ...
PMID:Competitive antagonists discriminate between NK2 tachykinin receptor subtypes. 216 37

Clonidine, noradrenaline and adrenaline (in the presence of propranolol), but not phenylephrine and methoxamine, stimulated an increase in the oxygen consumption of these slices that was blocked by yohimbine but not by prazosin. The stimulation was inhibited by ouabain and required the presence of Ca2+ in the incubation medium. The calcium ionophore A 23187 stimulated oxygen consumption in the tissue slices and enhanced the respiratory effect of clonidine. Atropine and (D-Pro2, D-Trp7.9)-substance P failed to block the respiratory response to clonidine in concentrations that inhibited the respiratory effects of carbachol and substance P, respectively. Release of acetylcholine from the unstimulated gland slices was reduced by clonidine or Ca2+ omission. Yohimbine prevented the clonidine effect and stimulated acetylcholine resting release. Nifedipine did not affect either the release of acetylcholine or the clonidine-induced reduction of acetylcholine release but blocked the oxygen uptake due to clonidine or to release acetylcholine.
 ...
PMID:Differentiation of alpha adrenoceptors mediating increase of oxygen consumption in rat submandibular salivary gland slices. 217 72

The different structures of the nasal, tracheal and bronchial vascular beds are described. All the vasculatures are influenced by neuropeptides released from three types of nerve: (1) sympathetic nerves release both noradrenaline and neuropeptide Y (NPY), both of which cause vasoconstriction; (2) parasympathetic nerves release both acetylcholine and either vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM) or peptide histidine isoleucine (PHI), all of which cause vasodilatation; and (3) sensory nerves release sensory neuropeptides such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinins A and B (NKA, NKB). Direct application of the neuropeptides to various preparations of the vascular beds confirms their actions. Stimulation of nerves to the airways in vivo causes vascular changes in the presence of anti-acetylcholine, anti-noradrenaline and ganglionic-blocking drugs, suggesting that they are mediated by neuropeptides. Reflex activation of the parasympathetic and sympathetic nerves to the airway vasculature has been established, but the relative importance of classical neurotransmitters and of neuropeptides has not been analyzed. The neuropeptides in sensory nerves are released when the nerves are stimulated by capsaicin, various chemical irritants and inflammatory mediators such as histamine and bradykinin. The sensory neuropeptides cause not only vasodilatation but also, in some instances, extravasation of plasma protein and an increase in interstitial fluid volume. The interaction of the different neuropeptide systems, and their interplay with classical transmitters released from motor nerves, require further exploration.
 ...
PMID:The NANC system and airway vasculature. 219 62


<< Previous 1 2 3 4 5 6 7 8 9 10