Abstract
In rat-1 fibroblasts stably expressing alpha1d-adrenoceptors BMY 7378, phentolamine, chloroethylclonidine and 5-methyl urapidil decreased basal [Ca2+]i. WB 4101 induced a very small effect on this parameter but when added before the other antagonists it blocked their effect. All these agents inhibited the action of norepinephrine. Phorbol myristate acetate also blocked the effect of norepinephrine and decreased basal [Ca2+]i. Staurosporine inhibited these effects of the phorbol ester. Our results suggest that: (1) alpha1d-adrenoceptors exhibit spontaneous ligand-independent activity, (2) BMY 7378, phentolamine, chloroethylclonidine and 5-methyl urapidil act as inverse agonists and (3) protein kinase C activation blocks spontaneous and agonist-stimulated alpha1d-adrenoceptor activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-1 Receptor Agonists
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Adrenergic alpha-1 Receptor Antagonists
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Adrenergic alpha-Agonists / pharmacology*
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Adrenergic alpha-Antagonists / pharmacology*
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Animals
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Calcium / metabolism*
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Cell Line
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Clonidine / analogs & derivatives
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Clonidine / pharmacology
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Dioxanes / pharmacology
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Dose-Response Relationship, Drug
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Endothelin-1 / pharmacology
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Fibroblasts
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Norepinephrine / pharmacology
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Phentolamine / pharmacology
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Piperazines / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / physiology
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Rats
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Receptors, Adrenergic, alpha-1 / physiology*
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Staurosporine / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology*
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Transfection
Substances
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Adra1d protein, rat
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Adrenergic alpha-1 Receptor Agonists
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Adrenergic alpha-1 Receptor Antagonists
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Adrenergic alpha-Agonists
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Adrenergic alpha-Antagonists
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Dioxanes
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Endothelin-1
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Piperazines
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Receptors, Adrenergic, alpha-1
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5-methylurapidil
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chlorethylclonidine
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(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
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Protein Kinase C
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Staurosporine
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BMY 7378
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Clonidine
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Tetradecanoylphorbol Acetate
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Calcium
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Norepinephrine
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Phentolamine