AJP - Renal Physiology, Vol 250, Issue 1 103-F108, Copyright © 1986 by American Physiological Society
Alpha 2-adrenoceptor stimulation and cellular cAMP levels in microdissected rat glomeruli
S. Umemura, D. D. Smyth and W. A. Pettinger
A functional role for the numerically predominant glomerular alpha
2-adrenoceptors is unknown. In other tissues, activation of alpha
2-adrenoceptors inhibits adenylate cyclase activity. We therefore examined
the effect of alpha 2-adrenoceptor stimulation with (-)-epinephrine (E) on
the cellular cAMP concentration in glomeruli isolated by microdissection.
Parathyroid hormone (1-34 PTH), prostaglandin E2 (PGE2), histamine,
serotonin, or adenosine, in the presence of 3-isobutyl-1-methylxanthine
(phosphodiesterase inhibitor) and propranolol, was used to activate
adenylate cyclase in single intact rat glomeruli. alpha 2-Adrenoceptors
were activated with varying concentrations of E (37 degrees C, 2 min). In
the presence of PTH-stimulated cAMP production, alpha 2-adrenoceptor
activation with E (5 X 10(-7) to 5 X 10(-6) M) suppressed cellular cAMP
levels in a dose-dependent fashion with the maximum at 30%. This
suppression by E was inhibited by 5 X 10(-6) M yohimbine but not by 5 X
10(-6) M prazosin, confirming alpha 2-adrenoceptor mediation of this effect
of E. Consistent with the above findings, the specific alpha 2-adrenoceptor
agonist BHT933 inhibited PTH-stimulated cAMP accumulation. E also inhibited
cAMP accumulation stimulated by serotonin. However, E did not suppress the
PGE2-, histamine-, or adenosine-stimulated increase in cellular cAMP in the
glomerulus. Activation of alpha 2-adrenoceptors inhibits cAMP formation
stimulated by PTH or serotonin but not by PGE2, histamine, or adenosine in
the rat glomerulus. Thus, the ability of alpha 2-adrenoceptors to inhibit
adenylate cyclase appears to be hormone and probably function specific.
