1. Cytosolic Ca2+ and phosphoinositide hydrolysis linked to constitutively active alpha 1D-adrenoceptors in vascular smooth muscle.
- Author
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Gisbert R, Pérez-Vizcaino F, Cogolludo AL, Noguera MA, Ivorra MD, Tamargo J, and D'Ocon P
- Subjects
- Adrenergic Agents pharmacology, Animals, Aorta drug effects, Aorta metabolism, Calcium Channel Blockers pharmacology, Guanethidine pharmacology, Hydrolysis, Rats, Rats, Wistar, Signal Transduction drug effects, Calcium metabolism, Inositol Phosphates metabolism, Muscle, Smooth, Vascular metabolism, Phosphatidylinositols metabolism, Receptors, Adrenergic, alpha-1 metabolism
- 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.
- Published
- 2003
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