Cyclic GMP-linked pathway for renin secretion.
The role of cGMP as a second messenger for renin secretion is contentious. This was investigated using a superfused collagenase-dispersed rat kidney cortex cell preparation devoid of indirect influences on renin secretion. Nitroprusside, atriopeptin II and 8-Br-cGMP all increased renin release but the dose-response relationships were biphasic. At low dose ranges there was a positive correlation between increasing drug concentration and renin secretion, but at high drug concentrations, a negative correlation was apparent. Methylene blue, a guanylate cyclase inhibitor, also suppressed baseline renin release at 10(-5) and 10(-6) M, but stimulated release at 10(-3) M. Using mid-range drug concentrations, the cGMP specific phosphodiesterase inhibitor MB22948 potentiated renin release in response to nitroprusside and 8-Br-cGMP. Inhibition of guanylate cyclase with either methylene blue or LY83583 attenuated renin release in response to nitroprusside, but, as expected, had no effect on 8-Br-cGMP induced release. We conclude that, under physiological conditions, cGMP is a stimulatory second messenger for renin release. This activity is mimicked at low dose ranges by 8-Br-cGMP, nitroprusside and atriopeptin II. In response to high doses of these drugs an unknown inhibitory pathway is activated and this opposes, in a dose-related manner, the stimulatory actions of cGMP for renin release.
Noble
A R
AR
Department of Physiology & Pharmacology, University of Southampton, England, United Kingdom.
Abu-Kishk
R A
RA
D'Aloia
M A
MA
Williams
B C
BC
Lush
D J
DJ
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008751:Methylene Blue / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010446:Peptide Fragments; D011688:Purinones / Q000494:pharmacology; D051381:Rats; D012083:Renin / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology
D000634:Aminoquinolines; D010446:Peptide Fragments; D011688:Purinones; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; C041715:6-anilino-5,8-quinolinedione; C062524:atrial natriuretic factor prohormone (103-125); D015106:3',5'-Cyclic-GMP Phosphodiesterases; D012083:Renin; D006162:Guanylate Cyclase; C011145:zaprinast; D006152:Cyclic GMP; D008751:Methylene Blue