The role of Ca2+ in the control of renin release from dog renal cortical slices.
Using a continuous superfusion system of dog renal cortical slices, we studied the role of Ca(2+) in the intracellular control mechanism for renin release. The calcium ionophore A23187 (10 microM) produced a significant decrease in renin release. This effect was abolished in the absence of extracellular Ca(2+). Moreover, pretreatment with the calmodulin inhibitor W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, 20 microM) completely prevented the inhibitory effect of A23187 (10 microM). The beta-adrenoceptor agonist isoproterenol (1, 10 and 100 microM) produced a concentration-dependent increase in renin release. Pretreatment with W-7 (20 microM) potentiated the stimulation of renin release induced by isoproterenol (1 microM). These results suggest that A23187-induced inhibition of renin release is mediated by the activation of calmodulin via an increase in intracellular Ca(2+) and beta-adrenoceptor-stimulated renin release is modulated by intracellular Ca(2+) mobilization.
Yatsu
Takeyuki
T
Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, 980-8578, Sendai, Japan. yatsu@yamanouchi.co.jp
Kurosawa
Hideo
H
Hayashi
Masahiko
M
Satoh
Susumu
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012083:Renin / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D007476:Ionophores; D013449:Sulfonamides; D000001:Calcimycin; C017967:W 7; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D012083:Renin; D007545:Isoproterenol; D002118:Calcium