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)

The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret. 128 77

1. Unilateral denervation of the rat vas deferens (RVD) was performed under anesthesia. The animals were allowed to recover 4 or 10 days and then concentration-effect (C-E) curves to noradrenaline (NA) and neurokinin A (NKA) were constructed in denervated and control RVD. 2. Tissues denervated 4 or 10 days produced NA responses shifted 20-fold to the left with maxima 130% of control. 3. NKA C-E curves in denervated RVD were not significantly different from control. 4. Phenylephrine exhibited a 6-fold increase in tissue sensitivity after denervation. 5. Chronic denervation of the vas deferens resulted in significant postsynaptic supersensitivity to alpha 1-adrenoceptor agonists but not to NKA.
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PMID:Absence of denervation supersensitivity to neurokinin A in the rat vas deferens. 135 59

We measured the intracellular free calcium ion concentration [( Ca2+]i) of acinar cells in isolated feline tracheal submucosal glands in response to secretagogues using the Ca2(+)-sensitive fluorescent dye fura-2. The secretagogues included cholinergic, adrenergic agonists, substance P (SP), and vasoactive intestinal polypeptide (VIP) which induce mucus glycoprotein secretion from feline tracheal submucosal glands. Methacholine (MCh) produced a significant increase in [Ca2+]i of up to 9.8 times that of control in a dose-dependent fashion at concentrations of 10(-8) to 10(-3) M. [Ca2+]i increase by MCh reached a peak within 30 s after stimulation and thereafter showed a sustained rise. In Ca2(+)-free medium, MCh produced an initial transient rise, which was less than 30% of that in a Ca2(+)-containing solution, and which lasted for 60 s with no prolonged sustained rise in [Ca2+]i. Atropine abolished MCh-evoked [Ca2+]i increase. Phenylephrine and SP produced a prolonged increase in [Ca2+]i without an initial transient increase. Phenylephrine (up to 10(-4) M) evoked an increase in [Ca2+]i by up to 240% that of control, which was abolished by prazosin. SP (up to 10(-4) M) also evoked an increase in [Ca2+]i by 155% that of control, which was abolished by atropine. By contrast, both isoproterenol (up to 10(-5) M) and VIP (up to 10(-5) M) failed to alter [Ca2+]i. These findings indicate that the mucus glycoprotein secretion evoked by muscarinic cholinergic, alpha-adrenergic agonist or SP can be mediated by intracellular Ca2+, whereas that by beta-adrenergic agonists or VIP cannot.
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PMID:Intracellular calcium concentration of acinar cells in feline tracheal submucosal glands. 170 76

1 Various doses of mediators were tested on tracheal vascular resistance in dogs anaesthetized with pentobarbitone. Tracheal vascular resistance was determined by perfusing the cranial tracheal arteries at constant flows and measuring inflow pressures. 2 All drugs produced dose-related changes in vascular resistance. 3 The peptides bradykinin, substance P and vasoactive intestinal peptide (VIP) each had similar vasodilator potencies and were much more powerful than histamine, methacholine and salbutamol. 4 Platelet activating factor (Paf) was a weaker dilator than the peptides. Prostaglandins D2, E1 and F2 alpha had wide dilator potency ranges, PGE1 being very effective even at low concentrations. 5 Phenylephrine, an alpha-adrenoceptor agonist, was the only drug tested that always increased vascular resistance. 6 All the drugs studied also had effects on the contralateral tracheal vascular resistance.
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PMID:Dose-related effects of pharmacological mediators on tracheal vascular resistance in dogs. 342 76

The bronchial arteries extend to all lung structures in man with the exception only of the alveolar wall. In addition to providing nutrition to the lungs, the bronchial vessels can also function as a hemodynamic and gas-exchange system due to anastomoses with the pulmonary arteries; they also play a significant role in controlling the clearance of chemical mediators, regulating the development of airway wall edema, and controlling heat exchange in the tracheobronchial tree. We have measured the effects of inflammatory and other mediators on tracheal mucosal thickness and the changes in tracheal vascular resistance in dogs. Bradykinin, histamine, and methacholine had large "vasodilator" effects, decreasing vascular resistance, and they also clearly increased the thickness of the mucosa. Substance P, VIP, PGF2 alpha, and PGE1 had as large a response on vascular resistance as the drugs mentioned above, but only had small effects in increasing tracheal mucosal thickness. Salbutamol fell between these 2 groups with regard to the pattern of response. Phenylephrine had an opposite action, causing an increase in vascular resistance and a decrease in mucosal thickness. Despite the vasodilatation and the increase in vascular permeability due to vasoactive drugs, the changes in mucosal thickness were rather small and could not be correlated with the decreases in vascular resistance due to the different drugs. Such changes are unlikely to have an appreciable effect on tracheal airway resistance. The change in mucosal thickness may be more significant in those parts of the airways where the ratio of change in mucosal thickness to the radius of adjacent lumen is large, such as the nose and small conducting airways.
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PMID:Effects of inflammatory and other mediators on airway vascular beds. 359 20

Miosis induced by surgical trauma is a frequent problem during extracapsular cataract surgery. In experimental surgery on rabbits, the inhibitory effect on pupillary constriction of cyclo-oxygenase inhibitors, local anesthetics, capsaicin (presumed substance P depletor), sympathomimetic agents, and anticholinergic agents were studied. In eyes predilated with tropicamide, iris massage caused marked pupillary constriction. Randomized pretreatment with the following agents significantly inhibited miosis: flurbiprofen, P less than 0.005; topical anesthetics (benoxinate, P less than 0.001, cocaine, P less than 0.05, proparacaine, P less than 0.005); and retrobulbar capsaicin, P less than 0.005. No significant inhibition was shown with topical indomethacin aqueous solution (P less than 0.15), topical tetracaine (P less than 0.15), or retrobulbar lidocaine (P less than 0.15). No single agent or combination of agents blocked the total miotic response; however, a combination of flurbiprofen, benoxinate, and capsaicin blocked more than two third of the miosis. Phenylephrine, a sympathomimetic (active) mydriatic agent, was more effective than anticholinergic (passive) mydriatic agents in obtaining maximal pupillary size after surgical iris massage.
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PMID:Inhibitors of surgically induced miosis. 713 42

The salivary flow elicited by phenylephrine was reduced in kininogen-deficient rats or by pretreatment of normal Wistar rats with HOE 140, a bradykinin antagonist. Salivary flow induced by substance P was similar in normal and kininogen-deficient rats. Phenylephrine released large amounts of kallikrein in saliva. Isoproterenol was less active while pilocarpine and substance P induced a small secretion of kallikrein. The saliva produced by anaesthetized rats in response to heat stress contained low levels of kallikrein. However a large depletion of the kallikrein content of submaxillary glands was observed in awake animals exposed to 36 degrees C and 40 degrees C for one hour. This depletion was suppressed by prazosin administered with a beta-adrenergic antagonist. Administered alone, these drugs had no effect, whereas atropine increased the depletion. The presence of kallikrein was observed in the oedema fluid which developed around the submaxillary glands in rats pretreated with atropine or exposed to 40 degrees C. A consumption of plasma kininogens occurred during heat exposure. The reflex-induced release of kallikrein during heat exposure is mainly controlled by sympathetic nerves through activation of both alpha and beta-adrenoreceptors. This release induces the formation of kinins which participate to the thermolytic salivation.
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PMID:The release of glandular kallikrein from submaxillary glands of rats exposed to heat. 752 66

1. The modulatory role of neuropeptide Y (NPY) on pulmonary oedema induced by acetylcholine and capsaicin was investigated. The effects of NPY on the haemodynamic response to acetylcholine, phenylephrine and substance P were also investigated. 2. Isolated, ventilated, exsanguinated lungs of the rabbit were perfused with a constant flow of recirculating blood-free perfusate. The double/arterial/venous occlusion method was used to partition the total pressure gradient (delta Pt) into four components: the arterial gradient (delta Pa), the pre- and post-capillary gradients (respectively delta Pa' and delta Pv') and the venous pressure gradient (delta Pv). Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). 3. Acetylcholine (10(-8) M to 10(-4) M) and substance P (SP, 10(-10) M to 10(-6) M) induced a concentration-dependent increase in the Kf,c. Capsaicin (10(-4) M) and 5-hydroxytryptamine (5-HT) (10(-4) M) also increased this parameter. NPY (10(-8) M) completely inhibited the effects of acetylcholine and capsaicin on the Kf,c, without preventing the effects of substance P and 5-HT. 4. Acetylcholine induced concentration-dependent vasoconstriction in the precapillary segment. The effect was inhibited by NPY and aspirin, an inhibitor of cyclo-oxygenase, while ketanserin, a 5-HT2 receptor antagonist, and SR140333, a new NK1 antagonist, had no protective effect. Phenylephrine increased delta Pa at high concentration, an effect also inhibited by NPY and aspirin. Substance P had no significant haemodynamic effect. When injected together with NPY, substance P (10(-6) M) induced a significant increase in the total pressure gradient. 5. It was concluded that NPY can protect the lung against acetylcholine- and capsaicin-induced oedemavia a prejunctional modulatory effect on the C-fibres. NPY also inhibits acetylcholine-evoked precapillary and phenylephrine-induced arterial vasoconstriction, probably by interfering with cyclo-oxygenase products synthesis.
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PMID:Modulatory effect of neuropeptide Y on acetylcholine-induced oedema and vasoconstriction in isolated perfused lungs of rabbit. 753 83

1. During heat exposure, rats secrete large amounts of saliva. Salivation started when body temperature exceeded 39 degrees C and was reduced by kininogen deficiency or by HOE 140, a bradykinin antagonist. This secretory response was associated with a partial depletion of glandular kallikrein from the submaxillary glands. The depletion was abolished by simultaneous treatment of the animals with an alpha- and a beta-adrenergic antagonist. During heat exposure, plasma levels of kininogens were reduced. 2. Pilocarpine and substance P induced a similar flow of saliva in normal and kininogen-deficient rats and released low amounts of kallikrein from salivary glands. Phenylephrine and isoproterenol induced a larger flow of saliva in normal rats than in kininogen-deficient rats. Both agents released large amounts of kallikrein in saliva but isoproterenol was only active at large doses. 3. During heat exposure, the blood content of submaxillary glands in normal as well as in kininogen-deficient rats increased as a function of the ambient temperature. This increase was suppressed by atropine and NG-nitro-L-arginine, a NO-synthase inhibitor, but was not modified by HOE 140. Simultaneously, a swelling of the glands and of the surrounding soft tissues occurred in normal but not in kininogen-deficient rats. Kallikrein was present in the edema fluid. 4. The kallikrein-kinin system would thus participate in heat-induced salivary secretion and kinins may be a factor responsible for electrolyte and water exchanges in the glands.
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PMID:Involvement of the kallikrein-kinin system in the salivary secretion elicited in rats by heat stress. 753 74

Rat parotid salivary gland acinar cells were transfected by CaPO4 precipitation using a plasmid containing a replication-defective simian virus (SV40) genome. Out of 30 clonal cell lines, 2 were shown to have moderate to high levels of cytodifferentiation and salivary gland acinar cell function. Functional studies with the two cell lines indicated that the beta-adrenergic agonist (isoproterenol), vasoactive intestinal peptide prostaglandin E1, and forskolin were effective activators of intracellular cyclic adenosine 3':5'-cyclic monophosphate production. Phenylephrine, carbamylcholine, and UTP were effective in increasing inositol phosphate production and intracellular free calcium levels, whereas substance P was without affect. Utilizing indirect immunofluorescence analysis, both cell lines were shown to express the SV40 large T antigen. Electron microscopic evaluation documented moderate to high levels of cytodifferentiation with the maintenance of tripartite junctional complexes, cellular polarization, and presence of moderate amounts of secretory granules and rough endoplasmic reticulum. The two cell lines had doubling times of 22 and 36 h, respectively.
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PMID:Development and characterization of SV40 immortalized rat parotid acinar cell lines. 954 37


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