The modulatory action of 5-hydroxytryptamine on sodium efflux: the barnacle muscle fibre as a model system.
A study has been made of the action of 5-hydroxytryptamine (5-HT) on the radio-sodium efflux from single barnacle muscle fibres. (i) Stimulation of the Na efflux by external application of 5-HT is seen in both unpoisoned and ouabain-poisoned fibres. (ii) Concentrations of 5-HT as low as 10(-9)M are effective. (iii) Characteristically, the response to 5-HT is prompt in onset, reaches a peak within 20 min and then decays rather rapidly. Fibres from certain barnacle specimens are sometimes unresponsive to 5-HT. Such fibres, however, can be rendered responsive by preinjecting into them the non-hydrolysable GTP analogue, Gpp(NH)p. The response of the ouabain-insensitive Na efflux to 5-HT depends on external Ca2+ and, to a certain extent, on external Na+. (i) The response to 5-HT is unaffected by prior external application of Ca2+ antagonists, viz. verapamil, Cd2+ and WB-4101. (ii) The calmodulin antagonist, trifluoperazine (10(-5)M), completely abolishes the response to 5-HT, even in fibres preinjected with Gpp(NH)p. (iii) Diphenylhydantoin is less effective than trifluoperazine (TFP). Whereas the receptor antagonist methysergide is ineffective, cyproheptadine is very effective. (i) Prior application of the phosphodiesterase inhibitor 1-propyl-3-methyl-7-(5-hydroxyhexyl)-xanthine (PMX) or the inhibitor 1-isoamyl-3-isobutyl-xanthine (IAX) augments the size of the response to 5-HT, but fails to stop the response from decaying. (ii) Augmentation of the response to 5-HT by IAX is seen despite the presence of 10(-5) M-TFP. Prior injection of Mg2+ or protein kinase inhibitor (PKI) leads to abolition or reduction of the response to 5-HT. These results demonstrate that barnacle fibres are a useful preparation for investigation the natriferic action of 5-HT. They also support the view that the response to 5-HT involves a receptor-adenylate cyclase complex and is the result of activation by newly formed cAMP of cAMP-dependent protein kinase.
Bittar
E E
EE
Chambers
G
G
D000818:Animals; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002707:Chlordiazepoxide / Q000494:pharmacology; D005576:Colforsin; D004146:Dioxanes / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007294:Inositol / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D001468:Thoracica / Q000187:drug effects / Q000502:physiology*
D002147:Calmodulin; D004146:Dioxanes; D004224:Diterpenes; D010726:Phosphodiesterase Inhibitors; D047428:Protein Kinase Inhibitors; D011985:Receptors, Serotonin; D005576:Colforsin; D012701:Serotonin; D006165:Guanylyl Imidodiphosphate; D007294:Inositol; D010042:Ouabain; D010672:Phenytoin; D002707:Chlordiazepoxide; D012964:Sodium; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D008274:Magnesium; D002118:Calcium