Phorbol diester modulates alpha-adrenergic receptor-coupled calcium efflux and alpha-adrenergic receptor number in cultured vascular smooth muscle cells.

Abstract:

:The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate was used to probe the role of protein kinase-C in the modulation of alpha-adrenergic receptor-coupled calcium efflux in cultured vascular smooth muscle cells derived from rabbit aorta. Exposure of cells to 12-O-tetradecanoyl phorbol-13-acetate for 6 minutes caused a concentration-related (maximum effect at greater than or equal to 10 nM) increase in calcium-45 efflux from preloaded cells. Maximum calcium-45 efflux stimulated by 12-O-tetradecanoyl phorbol-13-acetate was equivalent to maximum norepinephrine-stimulated calcium-45 efflux, and maximally effective concentrations of 12-O-tetradecanoyl phorbol-13-acetate and norepinephrine together were no more potent than either drug alone. Exposure of cells to 12-O-tetradecanoyl phorbol-13-acetate for periods of 1-24 hours resulted in complete loss of norepinephrine-stimulated calcium-45 efflux and a much slower, concentration-related reduction in alpha-adrenergic receptor number, with a maximum reduction of 50-60% at 12-O-tetradecanoyl phorbol-13-acetate concentrations greater than or equal to 10 nM. Twenty-four hours of exposure to 12-O-tetradecanoyl phorbol-13-acetate (10 nM) and norepinephrine (10 microM) together caused no greater reduction in [3H]prazosin binding than did norepinephrine alone. 12-O-tetradecanoyl phorbol-13-acetate had no effect on [3H]prazosin-binding affinity. These data suggest an important role for protein kinase-C in both the acute excitation-contraction coupling of vascular smooth muscle alpha-adrenergic receptors, and in the long-term modulation of vascular alpha-adrenergic receptor responsiveness.

journal_name

Circ Res

journal_title

Circulation research

authors

Colucci WS,Gimbrone MA Jr,Alexander RW

doi

10.1161/01.res.58.3.393

subject

Has Abstract

pub_date

1986-03-01 00:00:00

pages

393-8

issue

3

eissn

0009-7330

issn

1524-4571

journal_volume

58

pub_type

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