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)

Muscle strips from the fundus, trigonum and distal ureters obtained from children at operations for vesico-ureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and despite a partial atropine resistance the neurophysiological experiments indicated that the transmitter causing contraction of the detrusor muscle is acetylcholine. Imipramine, which is used in the treatment of enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The adrenergic innervation was very sparse except around the ureter orifices. No contractile alpha-adrenoceptors could be detected but beta receptor mediated relaxation was found, which was neither of the beta 1 nor beta 2 type. A third type of beta receptor is postulated. Peptidergic nerves containing vasoactive intestinal peptide, VIP, were demonstrated in a few nerve terminals running along bundles of smooth muscle. No nerves containing enkephaline, somatostatine or substance P were found. VIP affected the detrusor muscle indicating a possible role as a modulator of transmitter action, while substance P had no effect. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, whether it was induced by nerve stimulation, cholinergic drugs or a potassium rich solution, making it suitable for treatment of diurnal enuresis.
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PMID:Innervation of the child urinary bladder. 302 85

Muscle strips from the fundus, trigone, and distal ureter obtained from children at operation for vesicoureteric reflux were studied using histochemical and immunohistochemical methods, and electrical nerve stimulation in an organ bath. A rich supply of cholinergic nerves was found and the transmitter causing contraction of the detrusor muscle was regarded as being acetylcholine. The adrenergic innervation was very sparse except around the ureteric orifices. No contractile alpha-adrenoceptors could be detected but beta-receptor-mediated relaxation was found. The type was not beta 1 or beta 2, suggesting a third type of beta-receptor. Peptidergic nerves containing vasoactive intestinal peptide (VIP) were demonstrated in a few nerve terminals. No nerves containing enkephalin, somatostatin, or substance P were found. VIP affected the detrusor muscle, indicating a possible role as a modulator of transmitter action. Imipramine, used for enuresis, had no anticholinergic effect on the bladder in the doses used clinically. The anticholinergic and calcium antagonistic drug terodiline inhibited all muscle activity, making it suitable for treatment of diurnal enuresis.
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PMID:Urinary bladder innervation in children. 355 68

Cerebral blood vessels, arteries and veins, are invested with a dense plexus of perivascular nerve fibres containing noradrenaline, acetylcholine esterase vasoactive intestinal polypeptide (VIP), substance P and avain pancreatic polypeptide (APP). The majority of the noradrenaline and APP-containing fibres disappear within one week after sympathectomy, while the other nerve fibres remain. Pharmacological studies of feline pial arteries in vitro have shown the presence of alpha 2- and beta 1- adrenoreceptors mediating contraction and dilatation, respectively. Dilatation can also be obtained by acetylcholine activating muscarinic receptors and by VIP and substance P.
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PMID:Vascular autonomic nerves and corresponding receptors in brain vessels. 612 26

Adenylate cyclase was stimulated by prostaglandin E2 (PGE2) and parathyroid hormone-related protein (PTHrP) in both these types of fibroblast and by calcitonin gene-related protein (CGRP) in the human fibroblasts in vitro. PGE2 (1 microM), CGRP (1 microM), and PTHrP (1 microM) stimulated adenylate cyclase up to 50-fold, 10-fold and 9-fold, respectively. Calcitonin (CT), substance P (SP), interleukin-1 beta (IL-1 beta), and transforming growth factor-beta 1 (TGF beta 1) had no effect on adenylate cyclase in either fibroblast. Intracellular Ca2+ (iCa2+) was measured in individual fibroblasts from the periodontal ligament using Indo-1 and an adherent cell analysis and sorting interactive laser cytometer. Ionomycin (3 microM) caused a transient rise of iCa2+ in all human and canine fibroblasts tested. The mean percentage increase in iCa2+ in response to ionomycin was 820 and 840% for human and canine fibroblasts, respectively. The human fibroblasts responded to PGE2 (1 microM) by an increased iCa2+ concentration; the mean percentage increase in iCa2+ was 187%. SP caused a less pronounced increase in iCa2+ in the human fibroblasts (56%). CGRP and SP caused a similar response in the canine fibroblasts. The mean percentage increase in iCa2+ in response to SP and CGRP was 95 and 78%, respectively. PTH, PTHrP, platelet-activating factor, CT, and IL-1 beta had no effect on iCa2+ in either type of fibroblast. The data indicate that cAMP and calcium have roles as intracellular secondary messengers in the action of PGE2, SP, CGRP, and PTHrP in fibroblasts of human and canine periodontal ligament.
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PMID:Effects of hormones and cytokines on stimulation of adenylate cyclase and intracellular calcium concentration in human and canine periodontal-ligament fibroblasts. 750 23

Neutrophils express receptors for numerous phlogistons which, when occupied, trigger distinct signal-transduction pathways. Previous studies have shown that stimulation of neutrophils with chemoattractants induces shedding of the adhesive molecule L-selectin and increased expression of the beta 2-integrin CD11b/CD18. We determined the effect of ligation of classic, G-protein-linked chemoattractant receptors [C5a, interleukin-8 (IL-8), formylmethionyl-leucylphenylalanine (FMLP) and substance P], receptors for the Fc portion of IgG (Fc gamma receptors) and receptors for transforming growth factor beta (TGF beta) on expression of adhesive molecules by neutrophils and the stimulus-transduction mechanisms thought to mediate these changes. We were surprised to observe that occupancy of Fc gamma receptors by immunocomplexes (BSA-anti-BSA) stimulated increased expression by neutrophils of CD11b/CD18 at concentrations which did not affect L-selectin expression (EC50 9 micrograms/ml versus 350 micrograms/ml respectively, P < 0.00001, n = 5). In contrast, similar to previous studies, recombinant C5a, recombinant IL-8 and FMLP all stimulated increased expression of CD11b/CD18 (170-260% of basal, P < 0.001, n = 5) and shedding of L-selectin (56-75% reduction from basal, P < 0.001, n = 5) at similar concentrations and with similar potencies (EC50 = 2, 5, and 3 nM respectively). In contrast, neither TGF beta 1 nor, surprisingly, substance P affected expression of CD11b/CD18 or L-selectin. The regulation of expression of CD11b/CD18 or L-selectin in response to FMLP or immunocomplexes was unaffected by cytochalasin B (5 micrograms/ml) or the tyrosine kinase inhibitor tyrphostin-25 (25 microM). Although occupancy of both chemoattractant (FMLP) and Fc gamma receptors stimulated increments in the second messenger diacylglycerol, disruption of actin microfilaments by cytochalasin B enhanced diacylglycerol generation in response to FMLP but not in response to ligation of Fc gamma receptors. Moreover, both FMLP and immune aggregates provoked fluxes of intracellular Ca2+ concentration which differed with respect to both magnitude and kinetics and did not correlate well with regulation of adhesive-molecule expression. As upregulation of CD11b/CD18 is tightly linked to exocytosis of specific granules, these results suggest that shedding of L-selectin by activated neutrophils is not linked to exocytosis. These studies provide further evidence that receptors for chemoattractants and immunocomplexes on the neutrophil are linked to multiple signalling pathways.
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PMID:Immunocomplexes stimulate different signalling events to chemoattractants in the neutrophil and regulate L-selectin and beta 2-integrin expression differently. 751 72

Electrical stimulation of the sympathetic innervation evoked secretion of submandibular and parotid saliva. By changing the mode of stimulation from a continuous to an intermittent one the fluid response increased and glandular blood flow improved. The volumes from the submandibular glands were larger than those from the parotid glands and further, the protein concentration of submandibular saliva was higher than that of parotid saliva. Adrenaline, isoprenaline and phenylephrine evoked larger fluid responses from submandibular than from parotid glands. However, the fluid response was small compared to the parasympathetic one. Substance P-evoked saliva was used as carrier for protein released by sympathetic nerve stimulation or administration of adrenaline and isoprenaline. In vitro tissues of submandibular and parotid glands responded to adrenaline with a dose-dependent release of protein. Taken together, the analytical pharmacology performed in vivo and in vitro, and including the antagonists phentolamine, dihydroergotamine, propranolol and metoprolol, showed that in submandibular glands, alpha(alpha 1)adrenoceptors were predominantly involved in fluid secretion and beta(beta 1)-adrenoceptors predominantly involved in protein secretion. In parotid glands, fluid secretion seemed solely to depend on alpha(alpha 1)-adrenoceptors, while beta(beta 1)-adrenoceptors seemed almost solely involved in protein secretion.
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PMID:Fluid and protein secretion from ferret submandibular and parotid glands in response to sympathetic nerve stimulation or administration of sympathomimetics. 762 75

Nonadrenergic noncholinergic (NANC) contractile responses in guinea pig bronchi are due to the release of tachykinins from airway sensory nerves. The purpose of this study was to determine whether beta 2-receptor agonists modulate NANC contractions in guinea pig bronchi in vitro. Bronchial rings were suspended in organ baths for isometric measurement of tension, and comparable contractions were induced by electrical field stimulation (EFS; 40 V, 0.5 ms, 8 Hz for 20 s) or by exogenous substance P (3 microM). Aformoterol and salbutamol produced concentration-dependent inhibition of the NANC contraction, with aformoterol being ninefold more potent than salbutamol; approximate 50% inhibitory concentrations for aformoterol and salbutamol were 1.03 nM (n = 6) and 9.3 nM (n = 6), respectively. Aformoterol also inhibited the contraction induced by exogenous substance P but to a far lesser extent than its inhibition of EFS-induced responses. The inhibitory effects of formoterol (10 nM) on responses to EFS at 8 Hz were significantly prevented by propranolol (1 microM) and ICI 118551 (a beta 2-antagonist, 0.1 microM) but not by atenolol (a beta 1-antagonist, 1 microM) or phentolamine (10 microM). These experiments demonstrate that beta 2-agonists may modulate the release of tachykinins from airway sensory nerves by prejunctional receptors.
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PMID:Beta 2-adrenoceptor agonists inhibit NANC neural bronchoconstrictor responses in vitro. 768 10

Experiments were performed to investigate the presence and nature of beta-adrenoceptors in blood vessels supplying the posterior capsule of the rabbit knee joint. Electrical stimulation of the posterior articular nerve (PAN) and close intra-arterial injection of adrenaline produced vasoconstriction which reversed to vasodilatation with administration of the alpha-adrenoceptor antagonist phenoxybenzamine. In almost all animals close intra-arterial injection of the beta-adrenoceptor agonist isoprenaline resulted in vasodilatation. Injection of the more selective beta-agonists dobutamine, salbutamol and terbutaline also produced vasodilatation with a rank potency order of isoprenaline > dobutamine > salbutamol > or = terbutaline. The beta-adrenoceptor antagonist propranolol abolished the dilator responses to adrenaline and isoprenaline, and significantly reduced the dilator responses to PAN stimulation in phenoxybenzamine-treated animals. Nerve-mediated vasodilatation was also reduced by the substance P antagonist D-Pro4 D-Trp7,9,10 SP4-11, suggesting that substance P contributes to this dilatation. Dobutamine, a selective beta 1-agonist, produced vasodilatation which was abolished by administration of the selective beta 1-antagonist atenolol. Isoprenaline-induced vasodilatation was substantially reduced by atenolol. The dilator response to isoprenaline appeared to be unaffected by the selective beta 2-antagonist ICI118551, but the weak dilator responses to the selective beta 2-agonists salbutamol and terbutaline were significantly reduced by this antagonist. The results of this study suggest that beta-adrenoceptors appear to be involved in the sympathetic regulation of rabbit knee joint blood flow, and that this is predominantly mediated via beta 1-adrenoceptors.
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PMID:Sympathetic innervation and beta-adrenoceptor profile of blood vessels in the posterior region of the rabbit knee joint. 769

The expression of the alpha 6 beta 4 and alpha 6 beta 1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits alpha 6, beta 4, and beta 1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immuno-electron microscopy. The identity of these cells as LC was further established by coincident staining for alpha 6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-alpha (TNF alpha), the predominant cytokine in mast cell granules, also induced LC to express alpha 6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNF alpha antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce alpha 6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNF alpha in the regulation of the integrins alpha 6 beta 4 and alpha 6 beta 1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.
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PMID:Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells. 834 16

In the resting awake dog a continuous-wave Doppler flow transducer on the right bronchoesophageal artery inscribes a sharp early systolic spike and low flow in late systole and throughout diastole, indicating a highly resistive bed. An analysis of autonomic factors using intravenous, cumulative, and randomly applied cholinoceptor, beta 1- and beta 2-adrenoceptor, and alpha 1- and alpha 2-adrenoceptor antagonists indicates that the low vascular conductance is due to cholinoceptor and alpha 1- and alpha 2-adrenoceptor effects in a ratio 3.6:1. No beta-adrenoceptor tone is present. Sighing behavior invokes a transient (< 2 s) fall in intrapleural pressure (and thus rise in bronchovascular transmural pressure) of 10-30 mmHg, which is followed by a two- to threefold increase over 30 s in bronchial flow and conductance, an effect simulated in 50% of dogs when bronchovascular transmural pressure is acutely raised and maintained over 40-60 s by inflating an intra-aortic balloon distal to the origin of the bronchial artery. Autonomic blockade has no effect on bronchovascular dilatation evoked either by sighing or by balloon inflation. It is concluded that, in the resting bronchial circulation, there exists strong cholinoceptor and alpha-adrenoceptor-based vasoconstrictor activity which can be overpowered by strong nonadrenergic noncholinergic local vasodilator reflexes evoked by sudden changes in intrathoracic transmural pressure possibly acting on stretch-sensitive sensory nerve endings containing substance P, calcitonin gene-related peptide, and neurokinins. The tonic vasoconstrictor but not the sigh-evoked vasodilator effects are sensitive to pentobarbital sodium anesthesia.
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PMID:Control of resting bronchial hemodynamics in the awake dog. 836 67


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