Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of 5-hydroxytryptamine (5-HT) on the positive inotropic responses to catecholamines were investigated in isolated rabbit papillary muscles. 5-HT produced a concentration-dependent positive inotropic effect, an effect which was antagonized by prazosin, but not by propranolol. The positive inotropic effect of 5-HT diminished greatly in muscles from rabbits pretreated with 6-hydroxydopamine. Thus, it is likely that 5-HT causes a release of norepinephrine and increases force of contraction indirectly through alpha-1 adrenoceptors. In the presence of prazosin, 5-HT exerted a concentration-dependent inhibition of the positive inotropic response to isoproterenol. The positive inotropic responses to tyramine and a beta-1 adrenoceptor agonist T-1583 were also inhibited by the addition of 5-HT. The inhibitory effect of 5-HT on the beta adrenoceptor-mediated responses was unaffected by methysergide, ketanserin, ICS 205-930 or atropine. Pretreatment with pertussis toxin did not block the inhibitory effect of 5-HT on the inotropic response to isoproterenol, while abolishing the cholinergic interaction against the isoproterenol response. In contrast to its antagonizing effect on the inotropic response to isoproterenol, 5-HT produced an additive effect on the positive inotropic response to norepinephrine. However, when neuronal amine uptake was blocked by cocaine, the positive intropic response to norepinephrine was suppressed by the addition of 5-HT. 5-HT inhibited (-)-[125I]iodocyanopindolol binding to the membranes from rabbit ventricles with a monophasic displacement curve.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition by 5-hydroxytryptamine of the beta adrenoceptor-mediated positive inotropic responses to catecholamines in rabbit papillary muscles: direct interaction with beta adrenoceptors. 131 72

The mechanisms of action of two different serotonin receptors, found in a neuronal cell line (neuroblastoma X glioma hybrid cells) and in a non-excitable glioma cell line, were explored. In both cell lines, serotonin induced a dose-dependent, transient rise of cytosolic Ca2+ activity (measured by fura-2 or indo-1 fluorescence). Ca2+ channel blockers (Ni2+ and La3+, not nifedipine) suppressed the Ca2+ response to serotonin in the hybrid cells but not in the glioma cells. After application of Ca2+ ionophores (ionomycin and A23187) in order to short-circuit internal Ca2+ stores, serotonin was still able to induce a Ca2+ response in the hybrid cells but not in the glioma cells. Serotonin dose-dependently stimulated the rate of 45Ca2+ uptake several-fold in the hybrid cells, but hardly at all in the glioma cells. Thus, in the neuronal cell line cytosolic Ca2+ activity is raised through enhancement of Ca2+ entry into the cells from the extracellular environment via 5-HT3 receptors (blocked by ICS 205-930, MDL 72222 and GR 38032 F). The depolarization response caused by serotonin in the hybrid cells is due to activation of cation conductance(s), obviously allowing entry of extracellular Ca2+. In contrast to the neuronal cell line, in the glial cell line the rise of Ca2+ activity is mediated by ketanserin-susceptible 5-HT2 receptors (not affected by treatment with pertussis toxin) mainly liberating Ca2+ from internal stores. In the glioma cells the release of Ca2+ from internal stores leads to opening of Ca2+-dependent K+ channels, responsible for the hyperpolarizing response. Thus, the neuronal and the glial cell lines might provide suitable systems in which to study the diverse cellular functions triggered by the rise of cytosolic Ca2+ activity, which is caused by different serotonin receptors.
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PMID:Serotonin regulates cytosolic Ca2+ activity and membrane potential in a neuronal and in a glial cell line via 5-HT3 and 5-HT2 receptors by different mechanisms. 260 42

Serotonin (5-hydroxytryptamine, 5-HT) inhibited the formation of cAMP promoted by vasoactive intestinal polypeptide, plus forskolin, in mouse hippocampal and cortical neurons in primary culture. The rank order of potencies of classical 5-HT1 agonists in inhibiting cAMP formation in hippocampal neurons was 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) greater than 5-carboxamidotryptamine (5-CT) greater than d-lysergic acid diethylamide greater than 5-HT greater than 5-methoxy-N,N-dimethyltryptamine (5-MeO-N,N-DMT) greater than RU 24969 greater than ipsapirone greater than bufotenine greater than buspirone [half-maximal efficacy (EC50) = 7, 18, 30, 52, 90, 102, 100, 110, and 128 nM, respectively]. All the tryptamine derivatives substituted in position 5 of the indol were potent agonists [5-HT, 5-CT, 5-MeO-N,N-DMT, 5-methoxytryptamine, and bufotenine], whereas tryptamine, N-methyltryptamine, and N,N-dimethyltryptamine were poor agonists. The most potent antagonists tested were spiperone, (+/-)-pindolol, (+/-)-cyanopindolol, WB4101, and methiothepin, the affinity of spiperone for this receptor being 22 nM. In contrast, ketanserin, a specific 5-HT2 antagonist, and 5-HT3-selective drugs (ICS 205 930 and MDL 72222) were very weak in antagonizing the 5-HT-inhibited cAMP formation. The pharmacological profiles of 5-HT receptors mediating the inhibition of cAMP formation indicate that these receptors correspond to the 5-HT1A-binding site subtypes. Experiments with the Bordetella pertussis toxin indicate that the 5-HT1A receptor mediating inhibition of cAMP production involves a pertussis toxin-sensitive GTP-binding protein. In the absence of VIP, cAMP formation could be stimulated through a 5-HT receptor, but the specific 5-HT1A agonists, 8-OH-DPAT and RU 24969 did not stimulate cAMP production. These results suggest that in mouse embryonic hippocampal neurons, the 5-HT1A receptors, which are negatively coupled to adenylate cyclase, are distinct from the receptor positively coupled to this enzyme. The pharmacological characterization of the 5-HT receptor negatively coupled to adenylate cyclase in mouse embryonic cortical neurons indicates that it differs from the 5-HT1A receptor found in hippocampal neurons. Its main differences with the 5-HT1A receptor in hippocampal neurons are as follows: 1) 8-OH-DPAT was only a poor partial agonist in cortical neurons, whereas it was the best full agonist in hippocampal neurons; and 2) metergoline and methysergide as well as the anxiolytic drugs, ipsapirone and buspirone, which were potent agonists in hippocampal neurons, were competitive antagonists in cortical neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture. 282 13

The nonselective alpha-adrenergic agonist oxymetazoline inhibits parathyroid hormone (PTH)-stimulated cAMP production in intact OK cells, an epithelial cell line derived from an American opossum kidney. This inhibition, however, is not blocked by alpha 2-adrenergic receptor antagonists. After excluding several alternate hypotheses to explain this anomalous activity of oxymetazoline, we hypothesized that oxymetazoline activates a receptor in OK cells that is negatively coupled to adenylate cyclase but distinct from the alpha 2-adrenergic receptor. Prior exposure of OK cells to pertussis toxin blocks the inhibitory response to oxymetazoline, suggesting involvement of a guanine nucleotide-binding regulatory protein. Screening various compounds for attenuation of PTH-stimulated adenylate cyclase showed that serotonin (5HT) is a potent and fully efficacious agonist. Desensitization of alpha 2-receptor-mediated inhibition of cAMP production by epinephrine did not alter the response to either 5HT or oxymetazoline, indicating that these compounds do not produce their effect by activating alpha 2-adrenergic receptors. The 5HT1 receptor-selective antagonist methiothepin, but not ketanserin (5HT2-selective) or ICS-205,930 (5HT3-selective), blocked the response to both 5HT and oxymetazoline. The potency of methiothepin for antagonizing oxymetazoline-induced inhibition of PTH-stimulated cAMP production was not significantly different from its potency for the 5HT-induced effect. These data indicate that OK cells express a 5HT1 receptor that is negatively coupled to adenylate cyclase and that oxymetazoline is an agonist at these receptors.
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PMID:Oxymetazoline inhibits adenylate cyclase by activation of serotonin-1 receptors in the OK cell, an established renal epithelial cell line. 283 61

1. The effects of chronic in vitro administration of amitriptyline, a tricyclic antidepressant, on 5-hydroxytryptamine (5-HT) receptor-mediated adenylyl cyclase activity was studied in the neuroblastoma x glioma hybrid cell line, NG 108-15. 2. Treatment of NG 108-15 cells with 8 microM amitriptyline for 3 days increased forskolin-stimulated (0.1 microM) adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation. Addition of 5-HT (0.1-100 microM) increased forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells in a concentration-dependent manner. However, 5-HT did not affect forskolin-stimulated cyclic AMP accumulation in untreated cells. 3. The 5-HT4 receptor agonist, 5-methoxytryptamine, significantly enhanced forskolin-stimulated cyclic AMP accumulation in amitriptyline-treated cells. In contrast, amitriptyline treatment failed to modify 8-hydroxy-2-(di-n-propylamine) tetralin-induced inhibition of forskolin-stimulated cyclic AMP accumulation. 4. Pretreatment of cells with pertussis toxin did not affect the 5-HT-induced enhancement of cyclic AMP accumulation. 5. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells was attenuated by the 5-HT4 receptor antagonists, GR 113808 and ICS 205-930, with relatively low potency. However, spiperone, SCH 23390, and pindolol were completely ineffective against this 5-HT-induced enhancement. 6. Chronic treatment with amitriptyline did not modify the cyclic AMP production stimulated by prostaglandin E1 or cholera toxin. This treatment also had no effect on GTP gamma S-, NaF-, and Mn(2+)-stimulated cyclic AMP accumulation in isolated cell membranes. 7. Chronic treatment with the 5-HT receptor antagonists, pindolol or ICS 205-930, did not inhibit the 5-HT-induced enhancement of cyclic AMP accumulation.8. Chronic treatment with other antidepressant drugs, imipramine, mianserin or paroxetine, elicited the 5-HT-induced enhancement of cyclic AMP accumulation.9. Taken together, these results suggest that chronic amitriptyline treatment of NG 108-15 cells causes 5-HT to enhance forskolin-stimulated cyclic AMP accumulation by enhancing 5-HT receptor-mediated stimulation of adenylyl cyclase and not by reducing 5-HT-mediated inhibition of adenylyl cyclase. The 5-HT-induced enhancement of cyclic AMP accumulation in amitriptyline-treated cells may result from changes at the level of the 5-HT receptor rather than at the level of G, proteins or adenylyl cyclase. It is unlikely that this enhancement of cyclic AMP accumulation is caused by long-term antagonism of the 5-HT receptor by amitriptyline.
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PMID:Enhancement of cyclic AMP accumulation mediated by 5-HT after chronic amitriptyline treatment in NG 108-15 cells. 762 Jul 19

Electrical and pharmacological properties of currents induced by compounds having affinities for putative sigma receptors were investigated with NCB20 cells by use of the whole-cell patch-clamp technique. Antipsychotics and naloxone induced inward currents with a decrease in membrane conductance at a holding potential of -60 mV. The rank order of potency for compounds inducing these currents was bromperidol > haloperidol > mosapramine = clocapramine > carpipramine > chlorpromazine > remoxipride > naloxone. Sulpiride, which does not have affinity for sigma receptors, induced inward currents only slightly. Haloperidol-induced currents were not affected by the pretreatments with 10 microM of sulpiride, dopamine, atropine, N-methyl-D-aspartate, 2-amino-7-phosphonoheptanoic acid, morphine or A23187, 100 nM of ICS 205-930, 100 microM of forskolin, 1 microM of phorbol-12,13-dibutyrate, or 100 ng/ml of cholera or pertussis toxins. The reversal potential of the currents induced by haloperidol, naloxone or remoxipride was dependent on the concentration of external or internal potassium. These results indicate that the currents induced by the tested compounds are due to blockade of tonic, outward potassium currents and suggest that these agents act on putative sigma receptors and that the second messenger systems within the cell are not essential for the coupling between the receptors and the channels.
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PMID:Characterization of the currents induced by sigma ligands in NCB20 neuroblastoma cells. 791 Jan

Mouse neuroblastoma x rat glioma hybrid cells (N x G, NG108-15) were used to study the mechanism of Ca(2+)-current (ICa) inhibition by 5-hydroxytryptamine (5-HT). 5-HT caused a dose-dependent decrease of ICa which was abolished by ICS 205-930 (10)(-8) M) while 2-methyl-5-HT was an agonist. Intracellular infusion of GDP beta S (50 microM) prevented the 5-HT-induced inhibition of ICa whereas pertussis toxin (PTX) pretreatment did not alter the 5-HT response. The 5-HT-induced inhibition depended on the free Ca(2+)-concentration in the pipette solution. Pretreating N x G cells with low molecular weight (LMW) heparin (160 micrograms/ml), 200 microM ryanodine or 2-10 mM caffeine attenuated the 5-HT-induced inhibition of ICa. From these results we suggest that the 5-HT-induced ICa inhibition requires release of Ca2+ from intracellular stores.
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PMID:Role of intracellular Ca(2+)-stores in the 5-hydroxytryptamine-induced Ca(2+)-current inhibition in NG108-15 hybrid cells. 839 30