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)

A general model of the autonomic neuroeffector junction is proposed. In this model, emphasis is placed on the muscle effector bundle with electrotonic coupling between individual cells via gap junctions (or nexuses) and en passage release of transmitter from autonomic nerve varicosities. This release results in transmission to effector cells across junctional clefts ranging from about 20 nm in the vas deferens and iris to as much as 2000 nm in some large arteries. The ultrastructural identification of different autonomic nerve types is described. Current theories on the synthesis, storage, release, and inactivation of transmitter during cholinergic, adrenergic, and purinergic transmission are summarized. Some speculations are made about the possible involvement of purinergic nerves in the innervation of vessels and mast cells in the skin, and whether this involvement results in a functional link between ATP, histamine, bradykinin, and prostaglandin in cutaneous vasodilatation. Another possibility considered as the basis for this reflex is the release of substance P from sensory (pain) nerve collaterals in the skin.
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PMID:Autonomic neuroeffector junctions--reflex vasodilatation of the skin. 1 40

Benzalkonium chloride (BAC) is a mixture of quaternary benzyldimethylalkylammonium chlorides which was found to inhibit histamine release induced by polyamines (48/80, ATP, bradykinin, curare, guanethidine, polylysine, polymyxin B, poly-THIQ, protamine, stilbamidine or substance P), but not that caused by antigens, concanavalin A, dextran, lonophores (A23187 or X-537A), enzymes (chymotrypsin or phospholipase C), monoamines (dextromethorphan, meperidine or chlorpromazine) or detergents (decylamine, Triton X-100 or a fire ant venom alkylpiperidine). Inhibition by 1.5 and 3 microgram of BAC per ml caused parallel shifts of the 48/80 dose-response curves to the right with no loss of efficacy, indicating that the antagonism was surmountable. Phospholipase C was partially inhibited by BAC, but Triton X-100 also inhibited phospholipase C (but not 48/80), indicating that the inhibition of phospholipase C by BAC was probably a nonspecific, detergent effect. BAC caused histamine release by itself at concentrations over 5 microgram/ml. Heat inactivation (50 degrees C for 15 min) of the mast cells did not prevent this release, suggesting a lytic mechanism for this action. Structure-activity relations studies on various members of the BAC family for their ability to inhibit 48/80-induced histamine release indicated that benzyldimethyltridecylammonium chloride was the most potent.
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PMID:Benzalkonium chloride: selective inhibitor of histamine release induced by compound 48/80 and other polyamines. 9 63

Substance P, somatostatin, enkephalin and vasoactive intestinal polypeptide (VIP) did not mimic the inhibitory responses to non-adrenergic, non-cholinergic nerve stimulation. Substance P (0.1-10 microgram/ml) always caused contraction, enkephalin (0.1-10 microgram/ml) and somatostatin (0.1 microgram/ml) were inactive, while VIP (0.1-1 microgram/ml) produced very slow relaxation, taking about 4 min to reach a maximum after a latency of about 60 sec. Low concentrations of neurotensin (1-10 ng/mg) caused contraction, but at higher concentrations (50-1000 ng/ml) it produced a biphasic response which consisted of an initial contraction followed by a slow relaxation. In high tone preparations, the slow relaxation did not mimic the nerve-mediated response, taking approximately 43 sec. to reach maximum, after a long latency of about 15 sec. In contrast, ATP (0.1-50 microgram/ml) mimicked closely the rapid responses to non-adrenergic, non-cholinergic nerve stimulation in all preparations, whether the tone was low, medium or high. The time for the inhibitory response to reach maximum was about 15 sec after a latency of approximately 1 sec. Indomethacin (3.4-34 microgram/ml) did not unmask any inhibitory responses to any of the peptides. It is concluded that ATP remains the most likely substance to be the inhibitory transmitter released from non-adrenergic, non-cholinergic nerves supplying the smooth muscle of the taenia coli.
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PMID:Effects of neuronal polypeptides on intestinal smooth muscle; a comparison with non-adrenergic, non-cholinergic nerve stimulation and ATP. 42 25

During neointima formation, which is an early and essential step in the development of atherosclerosis, endothelium-independent relaxations (nitroglycerin, 3-morpholinosydnonimine) are preserved, whereas muscarinic endothelium-dependent relaxation becomes impaired. The present study was undertaken to determine the selectivity of this impairment. The neointima was induced by positioning a nonocclusive, soft silicone collar around the left carotid artery of rabbits. The contralateral artery served as a control. Seven days later, vascular rings were mounted in organ chambers, contracted with phenylephrine (0.35 microM), and cumulative dose-relaxation curves were made. Intima-bearing vessels were less sensitive to acetylcholine, confirming the original observation. In contrast, the dose-relaxation curves for substance P and for the calcium ionophore A23187 were not altered in the presence of neointima. The curve for ATP was even shifted to the left. These results suggest that the nitric oxide synthase: cyclic GMP system remains intact in intima-bearing vessels and that the diminished endothelium-dependent relaxations are due to a selective alteration of the muscarinic receptors.
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PMID:Selective muscarinic alterations of nitric oxide-mediated relaxations by neointima. 128 71

1. The effect of [D-Phe6] bombesin (6-13) methylester (OMe), a newly developed potent antagonist of bombesin receptors, has been investigated against bombesin-induced contractions of the guinea-pig and rat isolated urinary bladder. 2. Bombesin (0.1 nM-10 microM) produced a concentration-dependent contraction of the guinea-pig isolated bladder which approached the same maximum response as KCl (80 mM). The response to bombesin was antagonized in a competitive manner (rightward shift of the concentration-response curve without depression of the maximal response) by [D-Phe6] bombesin (6-13) OMe (0.3-10 microM). Degree of antagonism was concentration-dependent between 0.3 and 3 microM (dose ratios = 2.4, 9 and 39 in the presence of 0.3, 1, 3 microM of the antagonist). However, a larger concentration (10 microM) of the antagonist was not more effective (dose ratio = 36) than 3 microM. 3. Neither the action of bombesin nor the activity of the antagonist was influenced by peptidase inhibitors (bestatin, captopril and thiorphan 3 microM each) or by atropine, indomethacin, chlorpheniramine and desensitization of P2x purinoceptors by alpha, beta methylene ATP. 4. The bombesin antagonist was ineffective against contraction of the guinea-pig urinary bladder produced by the NK-1 tachykinin receptor-selective agonist, [Sar9] substance P sulphone. The action of the NK-1 receptor agonist was antagonized by L 668, 169 (3 microM), a cyclic peptide tachykinin antagonist. L 668, 169 had no effect toward bombesin-induced contraction. 5. The bombesin antagonist (1-10 microM) had no effect against the non-adrenergic non-cholinergic response of the guinea-pig isolated urinary bladder to electrical field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of [D-Phe6] bombesin (6-13) methylester, a bombesin receptor antagonist, towards bombesin-induced contractions in the guinea-pig and rat isolated urinary bladder. 132 41

Many studies suggest that smooth muscle relaxation caused by beta-adrenergic agents and various neuropeptides occurs as a result of an increase in cellular adenosine 3',5'-cyclic monophosphate (cAMP). However, the evidence is indirect, and furthermore does not demonstrate that an increase in cAMP is essential for mediating relaxation. To define more clearly the role of cAMP in receptor-mediated smooth muscle relaxation, we used a specific competitive antagonist of the action of cAMP on protein kinase A, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], and its S isomer, (S)-p-cAMPS, which functions as a cAMP agonist. In gastric smooth muscle cells from guinea pig, (S)-p-cAMPS caused a dose-related relaxation [50% inhibitory concentration (IC50) 86 +/- 59 nM]. Vasoactive intestinal peptide (VIP) produced smooth muscle cell relaxation (IC50 2.3 +/- 0.8 nM) through occupation of specific VIP receptors. (R)-p-cAMPS inhibited VIP-induced relaxation, with a rightward shift in the VIP dose-response curve, suggesting competitive antagonism. Furthermore, (R)-p-cAMPS inhibited relaxation induced by other agents that increase cellular cAMP (isoproterenol, calcitonin gene-related peptide, and glucagon) but not that induced by ATP or sodium nitroprusside. (R)-p-cAMPS had no effect on contraction stimulated by carbachol, cholecystokinin, or substance P. These data demonstrate that activation of protein kinase A is primarily responsible for mediating gastrin smooth muscle relaxation produced by adrenergic agents and various neuropeptides.
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PMID:A primary role for protein kinase A in smooth muscle relaxation induced by adrenergic agonists and neuropeptides. 132 27

The calcium current of frog sympathetic neurons has relatively rapid activation kinetics (tau < 3 ms) in response to changes in voltage. Pharmacologically, the current is blocked approximately 90% of omega-conotoxin, but < 10% by dihydropyridine antagonists. This suggests that nearly all of the current is N type. However, inactivation is slow and incomplete even for depolarizations lasting > 1 s, consistent with recent evidence that N-type channels do not always inactivate rapidly. The calcium current is partially inhibited via receptors for acetylcholine, luteinizing hormone releasing hormone, substance P, ATP, and norepinephrine. These effects are mimicked by internal dialysis with GTP-gamma-S, suggesting involvement of a G protein. The transmitters affect the activation kinetics of the calcium current in a voltage-dependent manner, which can be modeled as a reversible shift of some channels to "reluctant" states in which strong depolarization is needed to produce channel opening. The effects of transmitters develop and recover with t1/2 approximately 1-2 s, so if a second messenger is involved in receptor-calcium channel coupling, it must act rapidly.
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PMID:Separation and modulation of calcium currents in bullfrog sympathetic neurons. 133 98

The effects of electrical field stimulation (EFS) of rabbit middle cerebral arteries were examined using wire-mounted arterial segments. EFS of segments maintained at rest tension caused a tetrodotoxin-sensitive sympathetic contraction. In agonist-contracted segments maintained at approximately 60% of tissue maximum force, EFS caused a relaxation in two thirds of the preparations. Maximum response (mean +/- SEM) was 33 +/- 3.5% of maximal relaxation. The EFS relaxation was tetrodotoxin-sensitive but was not blocked by either chronic surgical sympathectomy or exposure to guanethidine (5 microM). Electron microscopy of chromaffin-fixed arterial sections showed the presence of chromaffin-positive large and small vesicles. Within the same sheath of Schwann were also a smaller number of nerve profiles containing many small clear vesicles. Removal of the vascular endothelium or treatment with atropine (10 nM) eliminated the EFS relaxation in approximately 50% of the segments and reduced the response in another 35-40%; in the remainder, relaxation was unaffected. Combined data for endothelium removal and atropine treatment showed that each caused a significant (p less than 0.01) reduction in the EFS relaxation. Atropine also significantly reduced EFS relaxation in guanethidine-treated segments. There was no reduction in EFS relaxation after procedures that antagonized ATP- or substance P-mediated relaxations. These results indicate that EFS of precontracted rabbit middle cerebral artery causes a neurogenic nonadrenergic relaxation. The neuroeffector mechanism mediating this response has a predominantly cholinergic endothelium-dependent component as well as a noncholinergic endothelium-independent component.
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PMID:Electrical field stimulation-mediated relaxation of rabbit middle cerebral artery. Evidence of a cholinergic endothelium-dependent component. 134 15

1. Whole-cell calcium currents of bullfrog sympathetic neurones were partially inhibited by noradrenaline (NA), chicken-II-luteinizing hormone-releasing hormone (LHRH), muscarine, ATP, substance P, or intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate)(GTP-gamma-S) or aluminium fluoride. These agents had similar effects on the activation kinetics of calcium current. 2. The amplitude of the LHRH effect varied from cell to cell. This did not correlate with cell size or the time of whole-cell dialysis. 3. The response to LHRH desensitized rapidly. Desensitization to LHRH did not affect inhibition by NA, ATP or substance P. 4. The effects of LHRH and NA were partially additive. 5. Cells dialysed with GTP-gamma-S still responded to NA or LHRH. However, NA or LHRH inhibited a smaller fraction of the calcium current than usual, and second applications of the same transmitter to GTP-gamma-S-dialysed cells were ineffective. 6. In GTP-gamma-S-dialysed cells, application of LHRH occluded the response to NA, but LHRH was still effective after application of NA. 7. The effect of GTP-gamma-S decreased during prolonged dialysis. 8. The effect of NA was selectively reduced by intracellular dialysis with the A-protomer of pertussis toxin (PTX), or extracellular pretreatment with high concentrations of whole PTX at room temperature. These treatments had little or no effect on the action of LHRH or ATP. 9. It is concluded that multiple G proteins can produce identical changes in calcium channel gating. The adrenergic receptor preferentially couples to a PTX-sensitive G protein.
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PMID:Calcium current modulation in frog sympathetic neurones: multiple neurotransmitters and G proteins. 135 63

Effects of neurokinin A (NKA) on sympathetic neurotransmission were studied in rat vas deferens. Although neither prazosin, an alpha 1-adrenoceptor blocker, nor alpha, beta-methylene adenosine triphosphate, a P2-purinoceptor blocker, inhibited the NKA-induced contractions in the epididymal site, high concentration of NKA-induced contractions in the prostatic site were slightly decreased by either of the two blockers. Treatment with guanethidine, which prevents the release of sympathetic transmitters from presynaptic nerve endings, also had no effect on NKA-induced contractions in either site. To investigate the effects of NKA on the adrenergic and purinergic neurotransmission in more detail, we measured transmitter release by using [3H]norepinephrine or [14C]adenosine. Neither spontaneous or nor evoked 3H efflux, indicating NE release, was affected by NKA in either site. NKA enhanced 14C efflux, indicating ATP release, evoked by electrical stimulation in the epididymal site, which may be originated from smooth muscle. In the prostatic site, contractions induced by electrical stimulation were enhanced in spite of no increase in 3H or 14C efflux. These results suggest that: 1) NKA has no effect on presynaptic nerve terminals in both sites, 2) NKA potentiates the effects of neurotransmitters in the prostatic site, and 3) NKA modulates the neurotransmissions.
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PMID:Postsynaptic potentiation of neurotransmission by neurokinin A in rat vas deferens. 135 17


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