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)

Ductal elements within salivary glands are responsible for modifying the electrolyte composition of primary saliva secreted by the acini. To study the mechanism and regulation of the transport processes involved requires a suitable preparation of functional ducts. To this end we have isolated intralobular ducts from rabbit mandibular salivary glands using the technique of tissue dissociation and microdissection. Light and electron microscopy demonstrated that the ducts corresponded ultrastructurally to striated intralobular ducts of the intact gland. Ducts could be maintained in tissue culture on polycarbonate filter rafts for up to 36 h, during which time the ends of the ducts did not usually seal. The overall resting content of ductal adenosine 3',5'-cyclic monophosphate (cyclic AMP) was 16.0 +/- 3.0 fmol mm-1 and increased dose dependently in response to stimulation with the beta-adrenoceptor agonist isoprenaline (10(-9)-10(-4) M; concentration required to produce a half-maximal response, K0.5 = 2.1 x 10(-6) M). The response to isoprenaline was blocked by the antagonist propranolol. Intracellular cyclic AMP content was also raised by the adenylate cyclase activator forskolin and by prostaglandin E2. Acetylcholine (3 x 10(-8)-10(-5) M) caused a dose-dependent and maintained rise in [Ca2+]i (K0.5 = 2.5 x 10(-7) M). This increase in [Ca2+]i could be reversed by the muscarinic antagonist atropine and appeared to result from a combination of mobilization of intracellular Ca2+ stores and entry of Ca2+ from the extracellular fluid. Noradrenaline induced only a very small, mainly transient rise in [Ca2+]i while phenylephrine failed to increase [Ca2+]i at all. Vasoactive intestinal peptide (5 x 10(-7) M) also produced a marginal, maintained rise in [Ca2+]i. Substance P, bombesin, isoprenaline, and prostaglandin E2 did not elevate [Ca2+]i. Application of the calcium ionophore ionomycin induced a substantial maintained rise in [Ca2+]i. Taken together, these results indicate that isolated and cultured striated ducts (i) possess intact beta-adrenoceptors coupled to adenylate cyclase, putative receptors for prostaglandin E2 and muscarinic receptors, and (ii) represent a viable preparation for the study of the transport mechanisms involved in the ductal modification of salivary fluid composition.
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PMID:Structural and functional characterization of striated ducts isolated from the rabbit mandibular salivary gland. 838 3

In the foot of the horse, arteriovenous anastomoses (AVAs) of epithelioid type occurred in the dermis of the coronary band, in the coronary and terminal papillae, in neurovascular bundles and at the entrance to and along the length of the dermal laminae. A particular feature of the epithelioid segment of AVAs in the horse, compared with that of other species, was the height and surface complexity of many of the endothelial cells. They extended into the lumen, forming undercut and tunnel-like areas which correlated with the characteristic surface marking of AVAs observed in vascular casts. The number of cell organelles, including the concentration of vesicles in the luminal cytoplasm, suggested cells with a high metabolic activity. The luminal surface possessed numerous microvilli and long cytoplasmic cell processes which appeared to surround material in the lumen. The innervation of AVAs was more dense than that of the arteries and consisted of adrenergic and peptidergic nerves. Noradrenaline- and neuropeptide Y-containing nerves were identified as the vasoconstrictor components of the nerve supply and occurred along arteries and formed dense plexuses around AVAs. Calcitonin gene-related peptide, substance P and vasoactive intestinal polypeptide are vasodilators and were present in single nerve fibres which accompanied arteries and AVAs along the length of the dermal laminae. In this study the distribution, density and innervation of AVAs in the equine foot are correlated with their proposed role in the development of acute laminitis. The release of vasoactive peptides from diseased organs remote from the foot may induce inappropriate prolonged dilatation of AVAs and thus contribute to the laminar ischaemia of acute laminitis.
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PMID:The structure, innervation and location of arteriovenous anastomoses in the equine foot. 857 98

1. Forearm blood flow responses to incremental challenges of acetylcholine and substance P, administered via the brachial artery, were measured by venous occlusion plethysmography in eight subjects in the presence of saline, the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine, and a control vasoconstrictor, noradrenaline. 2. Substance P and acetylcholine caused dosedependent increases in forearm blood flow (P < 0.001). When separated by 30 min saline infusions, repeated responses did not undergo tachyphylaxis. 3. Noradrenaline caused a mean reduction in basal blood flow of 34-51% (P < 0.001), and augmented the percentage increases in blood flow with both substance P (P = 0.05) and acetylcholine (P = 0.03) infusions. 4. NG-Monomethyl-L-arginine caused a mean reduction in basal blood flow of 42-45% (P < 0.001) and significantly inhibited the responses to both substance P (P < 0.001) and acetylcholine (P = 0.05). 5. In comparison with saline responses, NG-monomethyl-L-arginine caused a mean inhibition of 69 +/- 8% for substance P-induced vasodilatation and 40 +/- 5% for acetylcholine-induced vasodilatation. However, comparing responses with those to the control vasoconstrictor noradrenaline, NG-monomethyl-L-arginine caused a mean inhibition of 81 +/- 5% for substance P responses and 58 +/- 3% for acetylcholine responses. Inhibition by NG-monomethyl-L-arginine of the response to substance P was significantly greater than inhibition of the response to acetylcholine (P = 0.02). 6. Hence, in healthy men, a greater proportion of the forearm vasodilatation to substance P than to acetylcholine appears to be nitric oxide-mediated. Given its greater stability, substance P may be more suitable as a pharmacological tool in the investigation of stimulated nitric oxide production and endothelial cell function.
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PMID:Comparison of forearm vasodilatation to substance P and acetylcholine: contribution of nitric oxide. 949 1

Porcine galanin (1-29)-NH2, galantide (M15) and galanin (1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I used in concentrations of 300, 1,000 and 3,000 nM respectively caused contractions of rat fundus strips. The contractile responses to galanin(1-29)-NH2 were not modified by atropine (10 microM), guanethidine (10 microM), naloxone (1 microM), a mixture of propranolol (10 microM) and phentolamine (10 microM), indomethacin (10 microM), a mixture of mepyramine (10 microM) and cimetidine (10 microM), saralasin (10 microM), and spantide (100 microM). The effects of M15 and galanin(1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I were significantly decreased by atropine for 36 and 18% and by spantide for 37 and 26% respectively. Indomethacin inhibited the muscle response to M15 without influence on the galanin (1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I-induced action. These results support findings that galanin (1-29)-NH2 contracts rat gastric fundus strips by stimulating specific receptors localized on the surface of smooth muscle cells. M15 and galanin(1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I seem to contract smooth muscles not only by acting at galanin receptors, but by interacting with muscarinic or tachykinin receptors or modulating the release of acetylcholine and substance P. Diltiazem (EC50 825 nM), dantrolene (EC50 30.2 microM) and the phospholipase C inhibitors U-73122 (EC50 549 microM) and U-73343 (EC50 751 microM) lowered the contraction to galanin(1-29)-NH2 in a concentration-dependent manner. These observations imply that though the extracellular Ca2+ influx plays a major role in the action of galanin(1-29)-NH2, the release of Ca2+ ions from the intracellular stores contributes to the response of smooth muscles of galanin(1-29) NH2. Norepinephrine (30, 60, 100 and 300 nM) concentration-dependently reduced the Emax to galanin (1-29)-NH2 and reduced the slopes of the concentration-contraction curves, without a notable change in EC50. Pertussis toxin pre-treatment (10 and 30 mg/kg intravenous [i.v.]), 120 h before the experiment, notably increased the maximal response of the rat gastric fundus to galanin(1-29)-NH2, without a significant change in the properties of the concentration-contraction curves (EC50, slopes). The observations may suggest that pertussis toxin-sensitive GTP-binding proteins are involved in the modulation of the excitatory effects of galanin(1-29)-NH2 in the rat gastric fundus.
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PMID:Pharmacological characterization of the contractile effects of galanin (1-29)-NH2, galantide and galanin (1-14)-(alpha-aminobutyric acid8)scyliorhinin-I in the rat gastric fundus. 944 26

It is well known that transgenic mice expressing bovine growth hormone have altered neuroendocrine functions. Substance P was shown to influence the secretion of gonadotropins. In this investigation, the effect of a single injection of an antiserum to substance P was investigated in intact and castrated transgenic (MT-bGH) mice and in their normal litter mates. In the median eminence, the administration of antisubstance P serum resulted in a decreased dihydroxyphenyl acetic acid/dopamine index in intact and castrated normal mice but was without effect in transgenics. The homovanillic/dopamine index was decreased in normal mice (intact or castrated) but unchanged in transgenics. Norepinephrine and epinephrine were increased in normal mice (intact and castrated) treated with the anti-SP serum, but in transgenic mice, the anti-SP serum induced significant changes of norepinephrine only in intact animals, with no modifications in epinephrine levels. In the whole hypothalamus (minus the median eminence), the injection of antisubstance P serum resulted in an increased dihydroxyphenyl acetic acid/dopamine index in castrated, but not in intact, normal mice. In transgenic mice, this index was increased in intact but decreased in castrated animals. The homovanillic/dopamine index was decreased in normal intact mice treated with the antiserum but increased in intact transgenic mice. Norepinephrine and epinephrine were decreased by the antiserum treatment in normal intact mice but were unchanged in transgenics, except for norepinephrine in castrated transgenics, in which it was found increased. The administration of the antiserum did not affect plasma LH, FSH, or prolactin in normal mice but it reduced LH levels in intact transgenic mice. These results indicate that the response to the treatment with the antiserum to substance P shows considerable alterations in transgenic mice as compared with their litter-mate, normal controls, producing divergent effects on hypothalamic catecholamine metabolism. The present findings confirm that transgenic mice overexpressing the bGH gene have marked neuroendocrine alterations as compared with their normal litter mates.
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PMID:Effects of immunoneutralization of substance P on hypothalamic neurotransmitters in normal mice and in transgenic mice expressing bovine growth hormone. 957 54

The mechanisms of neurogenic relaxation in the longitudinal muscle of the isolated canine colon and its modification by enteric substances were investigated. Relaxations induced by transmural electrical stimulation with electrical pulses, nicotine or K+ in the muscle strips contracted with bradykinin and treated with atropine were attenuated but not abolished by NG-nitro-L-arginine (L-NA), and the inhibition was reversed by L-arginine. Oxyhemoglobin and ouabain inhibited the response, whereas K+ channel inhibitors, such as glibenclamide, tetraethylammonium, apamin and charybdotoxin, were without effect. In L-NA-treated strips, stimulation-induced relaxations were reduced by ouabain but not by oxyhemoglobin. Among substances tested, only norepinephrine, ATP, vasoactive intestinal peptide (VIP) and galanin produced relaxations. However, alpha- and beta-adrenoceptor antagonists and aminophylline did not alter the response to nerve stimulation. In the strips made unresponsive to VIP and galanin, stimulation-induced relaxations were not influenced. Indomethacin, calcitonin gene-related peptide, cholecystokinin, peptide YY, substance P and serotonin did not modulate the neurogenic response. It is concluded that the relaxation associated with nerve stimulation is mediated by nitric oxide (NO) synthesized from L-arginine and also by substance(s) activating the electrogenic Na+ pump but not that opening K+ channels. Norepinephrine, ATP, VIP and galanin can be excluded as candidate inhibitory neurotransmitters, and the substances used so far are unlikely to modulate inhibitory nerve function.
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PMID:Mechanism of neurogenic relaxation and modification of the response by enteric substances in isolated dog colon. 982 91

Reports on patients with hemiparalysis indicate the importance of the nervous system for the pathophysiology of rheumatoid arthritis (RA) or osteoarthritis (OA). Norepinephrine (NE) and opioids seem to be more antiinflammatory neurotransmitters whereas substance P is proinflammatory. The study aimed to investigate the direct noradrenergic nerve-immune cell interaction in human synovial membrane. We used a recently developed superfusion technique with electrical stimulation of synovial membrane to elicit local NE from synovial membrane slices. The readout parameter of synovial immune cells was interleukin-6 (IL-6). IL-6 was spontaneously secreted from RA and OA synovial membranes. Electrical field stimulation intensively reduced IL-6 secretion. In patients with OA or RA, this electrically induced reduction of IL-6 secretion was not significantly changed by alpha- or beta-adrenergic antagonists. The study demonstrates that local endogenous NE seem to play a minor role, which may be due to a depletion of NE or loss of noradrenergic fibers during chronic RA and OA.
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PMID:In vitro superfusion method to study nerve-immune cell interactions in human synovial membrane in long-standing rheumatoid arthritis or osteoarthritis. 1041 20

Noradrenaline- and peptide-containing nerve fibres project into the bone marrow and terminate in association with stromal cells and within the parenchyma. Peptidergic nerve terminals are also associated with antigen-processing and -presenting cells throughout the body and have been shown to be important in leucocyte trafficking and wound healing, as well as haemopoiesis. Here, we tested the in vivo effects of deleting the peripheral neuropeptide network on haemopoiesis and also investigated whether the target cell population for these substances was myeloid progenitor cells (colony-forming unit-granulocyte/macrophage, CFU-GM). Deletion of the neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) by capsaicin abrogates normal blood cell production. These neuropeptides produced significant stimulation of colony formation from unfractionated bone marrow and elicited production of soluble factors capable of stimulating highly enriched CFU-GM. CGRP also had a direct stimulatory effect on highly enriched CFU-GM. Noradrenaline elicited factors that inhibited colony formation and had no direct effect on CFU-GM. We conclude that the neuropeptides form the positive arm of a neural control system and that noradrenaline acts as a negative regulator.
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PMID:Neuropeptide control of bone marrow neutrophil production is mediated by both direct and indirect effects on CFU-GM. 1065 37

Vasomotor responses to various agonists were studied on isolated circular segments of human epicardial coronary arteries from three different age groups; 23-38 years, 40-58 years and 63-86 years. Noradrenaline had no or only weak contractile effect on coronary arteries from younger patients but induced contraction of all artery segments from older patients. The Emax value was significantly (P<0.0001) higher in arteries from the oldest group compared to each of the two younger age groups, whereas the potency was similar in all three groups. Linear regression analysis of noradrenaline-induced contraction in individual patients revealed a significantly positive age-correlation (correlation coefficient 0.67, P<0.0001). Contraction induced by endothelin-1 and relaxation induced by substance P, calcitonin gene-related peptide and vasoactive intestinal peptide on arteries precontracted with U46619 showed no significant differences in maximum responses and potencies between the three age groups, and no significant linear age-correlation. These data demonstrate a large variability in contractile responses to noradrenaline with contractions seen mostly in coronary arteries from older patients. It thus seems that sympathetic activation could contribute to coronary ischaemia in some patients.
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PMID:Influence of ageing on vasomotor responses of human epicardial coronary arteries. 1081 52

Ventricular septal (150-200 microm) arteries were isolated from the hearts of six-week-old CD-1 mice and mounted on a pressure myograph. Equilibration of the vessels at 70 mm Hg for 60 min resulted in the development of spontaneous myogenic tone. Maximum tone observed in these vessels greatly exceeded that previously reported in septal arteries from rats. Inhibition of endothelin ET(A) and endothelin ET(B) receptors with bosentan (1 and 10 microM) reduced basal tone. Endothelin release required intact endothelial cells. The alpha(1)-adrenceptor selective agonists phenylephrine and methoxamine did not cause change in coronary tone, while the alpha(2)-adrenceptor selective agonists 6-allyl-2-amino5,6,7, 8-tetrahydro-4H-thiazolo-[4,5-d]azepin-dihydrochloride (BHT 920) and clonidine produced vasodilatation. Noradrenaline (1 nM-10 microM) induced a concentration-dependent vasodilatation, which was inhibited by concurrent treatment with yohimbine (10 microM) and propranolol (20 microM). Vasodilatation due to BHT 920 was abolished with vessel denudation, indicating the endothelial location of alpha(2)-adrenoceptors. Acetylcholine (1 nM-10 microM) caused an endothelium dependent vasodilatation; inhibition of nitric oxide synthase with N(omega)-nitro-L-arginine methyl ester attenuated this response. The endothelium-dependent vasodilators bradykinin and substance P produced no vasomotor effect in mouse coronary arteries. Differences between human and murine responses may impact on the relevance of the mouse coronary artery for use as a potential model of human coronary vessel diseases.
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PMID:Endothelial and myogenic regulation of coronary artery tone in the mouse. 1113 53


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