Glyburide attenuates calmodulin antagonist-stimulated renin release from isolated mouse juxtaglomerular cells.
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 whether 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 microM) had no effect on basal RR, which measured approximately 10% or 30% of the total cellular renin activity after 4 or 24 h, 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 N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). Calmidazolium-stimulated RR returned to basal levels with 100 microM glyburide cotreatment. Blockade of voltage-gated calcium channels with verapamil or inhibition of calcium release from intracellular stores with 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (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.(ABSTRACT TRUNCATED AT 250 WORDS)
Linseman
D A
DA
Cardiovascular Pharmacology, Upjohn Laboratories, Kalamazoo, Michigan 49001, USA.
Lawson
J A
JA
Jones
D A
DA
Ludens
J H
JH
D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002469:Cell Separation; D005905:Glyburide / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012083:Renin / Q000378:metabolism*
D002147:Calmodulin; D007093:Imidazoles; C031938:calmidazolium; D012083:Renin; D007545:Isoproterenol; D005905:Glyburide