title: Activation of alpha-1A adrenoceptors mobilizes calcium from the intracellular stores in myocytes from rat portal vein.
abstract: Intracellular free Ca++ concentration ([Ca++]i) was monitored using the fluorescence from the dye fura-2-acetoxymethylester in single myocytes from rat portal vein. In the presence of oxodipine (a L-type Ca++ channel inhibitor), norepinephrine (10 microM) evoked transient increases in [Ca++]i which were related to release of Ca++ from intracellular stores. The alpha-1 adrenoceptors mediating intracellular Ca++ release and inositol phosphate accumulation were identified by using subtype-selective agonists and antagonists. Pretreatment with chloroethylclonidine had little effect on the norepinephrine-induced increase in [Ca++]i and inositol phosphate accumulation. In contrast, prazosin, 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane and alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)-amino )- propyl)benzeneacetonitrile fumarate produced a concentration-dependent inhibition of both intracellular Ca++ release and inositol phosphate accumulation. The rank of potency was prazosin > 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane > alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)-amino - propyl) benzeneacetonitrile fumarate. Methoxamine was as effective as norepinephrine but was less potent as shown by the rightward shift of the concentration-response curves. These results indicate that myocytes from rat portal vein express alpha-1A adrenoceptors whose activation stimulates phosphoinositide turnover and release of Ca++ from intracellular stores. The alpha-1A adrenoceptor stimulation of [Ca++]i and subsequent activation of Ca(++)-activated Cl- current was insensitive to intracellular applications of pertussis toxin, but concentration-dependently blocked by intracellular dialysis with a pipette solution containing anti-alpha q/alpha 11 antibody (whole cell recording mode).(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, URA CNRS 1489, Université de Bordeaux II, France.
authors.forename: N
authors.initials: N
authors.lastname: Lepretre
authors.forename: J
authors.initials: J
authors.lastname: Mironneau
authors.forename: S
authors.initials: S
authors.lastname: Arnaudeau
authors.forename: Z
authors.initials: Z
authors.lastname: Tanfin
authors.forename: S
authors.initials: S
authors.lastname: Harbon
authors.forename: G
authors.initials: G
authors.lastname: Guillon
authors.forename: J
authors.initials: J
authors.lastname: Ibarrondo
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000317:Adrenergic alpha-Antagonists; D000906:Antibodies; D018118:Chloride Channels; D007295:Inositol Phosphates; D018340:Receptors, Adrenergic, alpha-1; D002118:Calcium; D009638:Norepinephrine