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)

Electrophysiological recordings from freshly-dissociated smooth muscle cells from toad stomach revealed that substance P enhances one of two types of Ca2+ currents. That is, substance P enhances the slowly inactivating, high-threshold current but not the fast inactivating, low-threshold current. Acetylcholine has the same effect, but the acetylcholine action is blocked by atropine whereas the substance P action is not, indicating that the two agents act at different receptor sites. Thus, substance P, like acetylcholine, has a dual excitatory action on the smooth muscle cells employed in these studies, enhancing a specific type of Ca2+ current, as demonstrated here, and suppressing a voltage-sensitive K+ conductance, as previously described [Sims, S.M., Walsh, J.V., Jr. & Singer, J.J. (1986) Am. J. Physiol. 251, C580-C587].
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PMID:Substance P, like acetylcholine, augments one type of Ca2+ current in isolated smooth muscle cells. 247 1

Acetylcholine, substance P and nitroglycerin applied intra- and extraluminally to the perfused dog femoral artery segment with endothelium caused depressor responses. Endothelium denudation abolished the responses to acetylcholine and substance P. EC50 ratios of extra- versus intraluminal acetylcholine and substance P were 43 and 79, respectively, whereas those of nitroglycerin did not differ. Physostigmine potentiated the response to extraluminal acetylcholine. Acetylcholine seems to be degraded partly by cholinesterase in the arterial wall. Acetylcholine and substance P applied extraluminally are expected to reach the endothelium and release endothelium-derived relaxing factor.
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PMID:Extraluminally applied acetylcholine and substance P on the release of EDRF. 247 88

Basal release of vasoactive intestinal polypeptide (VIP) was 100-fold higher than substance P (SP) release from the vascularly perfused, neurally isolated canine small intestine. High-frequency field stimulation increased SP release but decreased VIP release. VIP release was markedly reduced by tetrodotoxin, perfusion with Ca-free medium, or by hexamethonium but not by atropine. Acetylcholine increased VIP output by an atropine-sensitive mechanism. Methionine-enkephalin or dynorphin (at 10-fold higher concentrations) markedly reduced VIP output; the actions of both these were abolished by naloxone. BHT-920, an alpha 2-adrenoceptor agonist, reduced VIP output markedly by a rauwolscine-sensitive mechanism. Isoproterenol and phenylephrine were without effect. Motilin produced persistent inhibition of VIP output. Thus VIP neurons of isolated canine small intestine were continuously active, driven by intrinsic cholinergic nerves, and subject to presynaptic inhibition by opioid agonists, alpha 2-adrenoceptor agonists, and motilin. This intrinsic neural system may provide tonic inhibitory control to the small intestinal circular muscle and provide a mechanism by which agents may modulate intestinal motor function.
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PMID:Release of VIP and substance P from isolated perfused canine ileum. 247 29

Acetylcholine and substance P applied to the donor tissue, dog femoral artery segments with endothelium, produced moderate relaxations of the assay tissue, endothelium-denuded dog coronary artery strips. The relaxation was attenuated markedly by treatment of the assay tissue with hydroquinone and abolished by oxyhemoglobin or methylene blue. In this bioassay system, the effect of AA861 and TMK777, new 5-lipoxygenase inhibitors, was evaluated. When the donor tissue was treated with AA861 or TMK777, the responses to acetylcholine and substance P were attenuated moderately, whereas the relaxation by nitroglycerin was not influenced by AA861. However, the inhibitors when infused just below the donor tissue did not attenuate relaxant responses to acetylcholine and substance P. Application of superoxide dismutase (SOD) to the donor tissue caused a relaxation of the assay tissue, and potentiated the relaxation by acetylcholine and substance P. AA861 and TMK777 suppressed the relaxant responses to acetylcholine and substance P, respectively, in the presence and absence of SOD to a similar extent and abolished the SOD-induced relaxation. Pyrogallol abolished the relaxation by acetylcholine, but did not inhibit the response when the donor tissue was pretreated with SOD. Therefore, it appears that AA861 and TMK777 do not degrade endothelium-derived relaxing factor (EDRF) in the perfusate via generation of superoxide anion or block the action of EDRF on vascular smooth muscle, but interfere with the synthesis and/or release of EDRF. The findings obtained so far support the idea that lipoxygenase products participate in the generation of EDRF.
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PMID:Possible involvement of 5-lipoxygenase products in the generation of endothelium-derived relaxing factor. 247 45

Canine and human coronary arteries were studied in organ baths to compare the responses to acetylcholine and serotonin in the two species. The human coronary rings were isolated from seven patients without cardiac disease (mean age 15 years, range 7-20). In one set of experiments canine and human preparations were incubated with phentolamine, propranolol and ketanserin (all at 1 mumol.litre-1 concentration) and precontracted with prostaglandin F2 alpha (PGF2 alpha 1-2 mumol.litre-1). Acetylcholine (0.1-10 mumol.litre-1) and serotonin (0.1-100 mumol.litre-1) relaxed canine preparations dose dependently, the maximum responses (expressed as % of depression of PGF2 alpha response) being 84 (SEM 6)% (n = 9) and 51(5)% (n = 6) respectively. In the same experimental conditions, acetylcholine and serotonin failed to relax the human coronary rings (n = 11) while substance P and bradykinin induced relaxations of 72(4)% (n = 11) and 66(7)% (n = 11) of PGF2 alpha response respectively. In another set of experiments, dose-contraction curves were constructed for acetylcholine or serotonin (in presence of phentolamine and propranolol). On human rings with endothelium, methylene blue (10 mumol.litre-1), a non-specific inhibitor of endothelium derived relaxing factor (EDRF), potentiated these dose-contraction curves: markedly for serotonin, the EC50 decreasing from 1.2(0.2) to 0.22(0.08) mumol.litre-1 (n = 11, p less than 0.01) with a significant increase in the maximal response); and slightly for acetylcholine, EC50 decreasing from 0.84(0.11) to 0.40(0.13) mumol.litre-1 (n = 10, p less than 0.05) without significant change in the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of responses to acetylcholine and serotonin on isolated canine and human coronary arteries. 248 33

Peptide-containing nerves have been examined in the rat femoral artery and vein using immunocytochemical and vasomotor techniques. The general neuronal marker PGP 9.5 revealed a moderate supply of nerve fibres and fascicles forming a loose network in the adventitia and the adventitial-medial border of the artery and vein. The majority of the nerve fibres in both the artery and vein displayed immunoreactivity for neuropeptide Y (NPY) and tyrosine hydroxylase (TH). The distribution pattern and number of these two types correlated well. The artery had a slightly richer PGP 9.5- immunoreactive nerve supply compared to the vein, but the nerve plexus in the vein displayed a more uniform arrangement. In contrast, relatively few nerve fibres displayed calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide immunoreactivity in either the artery or vein. The calcitonin gene-related peptide immunoreactive fibres had a similar distribution to that of the substance P containing fibres. Using a sensitive in vitro method the vasomotor responses to perivascular peptides were characterized. In the femoral artery NPY potentiated alpha 1-adrenoceptor mediated contractions, and had very little effect by itself. In contrast, 10(-7) M NPY contracted femoral veins by up to 68% relative to 60 mM potassium induced contraction, and there was no potentiation of alpha-adrenoceptor mediated contractions. Acetylcholine, peptide histidine isoleucine, vasoactive intestinal peptide, substance P and calcitonin gene-related peptide, all relaxed the contracted femoral artery and vein. Regarding the putative parasympathetic neurotransmitters, acetylcholine caused stronger relaxation of veins as compared to arteries whereas for vasoactive intestinal peptide and peptide histidine isoleucine the relaxations were stronger in the arterial preparation. These three agonists were more potent in the femoral vein. Substance P was more potent on the femoral vein, having the same maximum response in both preparations. On the other hand, the response induced by CGRP was some three times greater in the venous than in the arterial preparation. These data reveal that although there appear to be only minor differences in the peptidergic innervation of the rat femoral artery and vein pronounced differences occur in the peptide effector responses. The data support the concept that perivascular peptides play different roles in regulating various parts of the circulation.
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PMID:Peptide-containing nerves in the rat femoral artery and vein. An immunocytochemical and vasomotor study. 248 49

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

Putative neurotransmitters of the lower urinary tract were investigated in apes, rabbits and cats using immunohistochemical techniques of PAP (Peroxidase antiperoxidase) staining and IGSS (Immunogold silver staining) methods for Neuron specific enolase (NSE), Acetylcholine (Ach), Noradrenaline (NA), Vasoactive intestinal polypeptide (VIP), Substance P (SP) and Calcitonin gene related peptide (CGRP). 1) The localization of pelvic ganglions exhibited more striking evidence of species difference. Huge pelvic ganglions were found particularly in the dorsolateral area of the prostate in apes. On the other hand, in cats and rabbits, many ganglion cells were found around the uretero-vesical junctions. 2) In the pelvic ganglions of the apes, Ach immunoreactives were detected in nearly 70 percent of the cell bodies. 10-15 percent were NA immunoreactive cells. In addition, 15-20 percent VIP and a smaller percentage of SP immunoreactive cells were detected in the same ganglions. Axons extending from the ganglion cells showed the intense neurotransmitters immunoreactivity. 3) In the apes, varicose fibers containing SP were widely distributed in the epithelium, submucosa, muscle layer, and around the vessels of the bladder. SP immunoreactive cell bodies were found in the dorsal root ganglion at levels of L7, S1 and at the same levels in the posterior horn. On the other hand, the bulbourethral gland and the seminal vesicle contained SP immunoreactive cell bodies. 4) CGRP containing fibers were distributed in similar locations as SP containing fibers in the bladder. 5) VIP immunoreactive fibers were also widely distributed, being most dense at the base of the bladder.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunohistochemical studies of putative neurotransmitters in the lower urinary tract]. 257 46

Stimulation of autonomic nerves supplying smooth muscle tissues often evokes either an e.j.p. or an i.j.p. which involves a shift in the membrane potential such that the entry of calcium into the cell through voltage-sensitive calcium channels is likely to be increased or decreased respectively. In smooth muscle which freely discharges action potentials either spontaneously or in response to excitatory influences in vivo, the change in membrane potential will alter the rate of action potential discharge and so the tension developed by the smooth muscle. In this way there is modulation of the rate of entry of calcium, or its release within the cell, by a voltage-dependent mechanism entrained by the junction potential, as the action potential represents the operation of voltage-dependent calcium channels. In smooth muscles not freely discharging action potentials, the numbers of open calcium channels may change with depolarization, or even hyperpolarization, so the junction potential again brings into play a voltage-dependent mechanism of calcium entry. However, a dual mechanism of neurotransmission seems to operate at many autonomic nerve-smooth muscle junctions such that voltage-independent mechanisms coexist with voltage-dependent mechanisms. It is now generally accepted that activation of receptors on smooth muscle cells caused by bathing smooth muscles in solutions containing excitatory transmitters can bring into operation processes which are not voltage-dependent and which do not depend on modulation of the rate of action potential discharge. Up to the present it has been by no means certain that when released from autonomic nerves these excitatory transmitters (ACh, noradrenaline, substance P and n.a.n.c. excitatory transmitters) could also act in the same voltage-independent way - not least because studies of smooth muscle cells at the cellular level have been dominated by membrane potential recording (by micro-electrode) which has revealed the e.j.p. or some form of depolarization as a seemingly ubiquitous feature of excitatory autonomic junctions of nerve and smooth muscle cells. However, experiments show that under conditions when the e.j.p. and/or the action potential are abolished or severely impaired by drug application, substantial nerve-evoked smooth muscle contractions may occur at many autonomic junctions. Conversely, severe impairment of nerve-evoked contraction may occur in some cases with excitatory-receptor antagonists without loss, or even in some cases any impairment, of the e.j.p. which presumably depends on a different receptor type.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Are junction potentials essential? Dual mechanism of smooth muscle cell activation by transmitter released from autonomic nerves. 286 46

Vasomotor reactivity of human pial veins, obtained in conjunction with neurosurgical operations, was studied in vitro. The effect of transmitters in nerves previously recognized in these vessels, as well as that of neuromodulators, was characterized. A comparison of these effects with their effects in the nearby pial arteries of the same patients was made. It was found that the veins were equipped with more sensitive alpha-adrenergic receptors (lower EC50 values) than the arteries. The reverse was found for 5-hydroxytryptamine. Acetylcholine, which causes an endothelium-dependent dilation of pial arteries, contracted the veins despite an apparently intact endothelium. Considering the lower maximum values in veins, responses to histamine, the neuropeptides calcitonin gene-related peptide, bradykinin, and neuropeptide Y; and prostaglandins (PGE1 and PGF2 alpha) were principally the same in the arteries and veins. The dilatory responses to vasoactive intestinal polypeptide and substance P were less pronounced in veins than in arteries. The veins only transiently contracted to a depolarizing potassium solution; calcium influx promotors and inhibitors, as well as calcium-free solution, did not affect the contractile ability of the vein, contrasting to the reactivity of the artery. This clearly indicates that the veins are not substantially dependent upon calcium influx for their acute contractile ability.
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PMID:Vasomotor effects of neurotransmitters and modulators on isolated human pial veins. 288 77


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