title: Cytosolic Ca2+ and phosphoinositide hydrolysis linked to constitutively active alpha 1D-adrenoceptors in vascular smooth muscle.
abstract: In the present study, we analyzed changes in intracellular Ca2+ levels and inositol phosphate accumulation related to a population of alpha 1d-adrenoceptors in rat aorta resembling constitutively active receptors. Following intracellular Ca2+ store depletion by noradrenaline in Ca2+-free medium and removal of the agonist, restoration of extracellular Ca2+ induced four signals: a biphasic (transient and sustained) increase in [Ca2+]i, inositol phosphate accumulation, and a contractile response in the aorta. The transient increase in Ca2+, the inositol phosphate accumulation, and the contractile response were not observed in aortae incubated with prazosin or BMY 7378 [8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione] (a selective alpha 1d-adrenoceptor ligand), relating the three signals to alpha 1d-adrenoceptor activity. In the presence of nimodipine, only the sustained increase in Ca2+ and the inositol phosphate accumulation were observed, relating both signals to calcium entry through L-channels. The four signals were abolished by Ni2+. In the rat tail artery, where alpha 1d-adrenoceptors are not functionally active, restoration of extracellular Ca2+ after store depletion induced only a sustained increase in [Ca2+]i without inositol phosphate accumulation nor contractile response. Taken together these results suggest that in the aorta, Ca2+ entry is required for the recovery of cytosolic calcium levels and the display of the membrane signals related to the constitutive activity of alpha 1d-adrenoceptors, i.e., inositol phosphate formation and Ca2+ entry through L-type channels, which maintains a contractile response once the agonist has been removed.
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia, Universitat de Valencia, Burjassot, Valencia 46100, Spain.
authors.forename: Regina
authors.initials: R
authors.lastname: Gisbert
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez-Vizcaino
authors.forename: Angel L
authors.initials: AL
authors.lastname: Cogolludo
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Noguera
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Ivorra
authors.forename: Juan
authors.initials: J
authors.lastname: Tamargo
authors.forename: Pilar
authors.initials: P
authors.lastname: D'Ocon
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C547721:Adra1d protein, rat; D018663:Adrenergic Agents; D002121:Calcium Channel Blockers; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D002118:Calcium; D006145:Guanethidine