Glyburide attenuates calmodulin antagonist-stimulated renin release
from isolated mouse juxtaglomerular cells.
Linseman, Daniel A., Judy A. Lawson, David A. Jones, and James H.
Ludens.
Cardiovascular Pharmacology, Upjohn Laboratories, The Upjohn
Company, Kalamazoo, Michigan 49001
APStracts 2:0043F, 1995.
Previous reports have shown that K+ channel openers elevate plasma
renin activity in vivo and stimulate renin release (RR) from
juxtaglomerular (JG) cells in vitro. Therefore, we examined if the K+
channel blocker, glyburide, inhibits basal RR or RR stimulated by
elevating cAMP or by inhibiting Ca2+/calmodulin activity, in cultures
of isolated mouse JG cells. Glyburide treatment (10-300 [mu]M) had no
effect on basal RR which measured approximately 10% or 30% of the
total cellular renin activity after 4 or 24 hours, respectively. RR
stimulated by elevating cAMP with isoproterenol, forskolin, or 3
-isobutyl-1-methylxanthine, was also unaffected by glyburide. In
contrast, glyburide significantly attenuated RR stimulated by the
calmodulin antagonists, calmidazolium, trifluoperazine, and W-7.
Calmidazolium-stimulated RR returned to basal levels with 100 [mu]M
glyburide cotreatment. Blockade of voltage-gated calcium channels
with verapamil or inhibition of calcium release from intracellular
stores with TMB-8 had no effect on the ability of glyburide to
attenuate calmidazolium-stimulated RR. However, lowering of the
extracellular calcium concentration by the addition of EGTA abolished
the inhibitory effects of glyburide. We conclude that modulation of
K+ channels may influence RR by affecting Ca2+/calmodulin-regulated
secretion, but not cAMP-mediated secretion, from JG cells.
Furthermore, the inhibitory effects of K+ channel blockers on RR are
dependent on extracellular calcium.
Received 12 January 1995; accepted in final form 15 March 1995.
APS Manuscript Number F009-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.