Effect of cAMP analogues on glomerular inulin space of isolated rats renal glomeruli.
Cyclic AMP has been generally recognised as activator of cAMP-dependent protein kinases. However, there is little evidence about role of cAMP-dependent protein kinase (PKA), in particular izoenzymes PKA-I and PKA-II, in glomeruli contractility. We measured changes of glomerular inulin space (GIS) as a marker of its contractility in the presence of phosphodiesterase resistance cAMP analogues; activators and inhibitors of PKA. Activator of PKA i.e. (Sp) 8-Cl-cAMPS (0.1-100 microM) decreased GIS. (Rp) 8-Cl-cAMPS (0.1-100 microM), inhibitor of PKA, was ineffective but shifted concentration-response curve of (Sp) 8-Cl-cAMPS to right at 50 microM. Specific A site activation by N6-benzoyl-cAMP decreased GIS with maximum at 0.1 microM. Activation of B site by 8-aminobutyloamino-cAMP (0.1-100 microM) had no effect. However, specific activation of both sites on PKA-I or PKA-II by site-selective analogue pairs e.g. 8-aminobutyloamino-cAMP plus 8-piperidino-cAMP or N6-benzoyl-cAMP plus 8-piperidino-cAMP respectively, significantly increased sensitivity of glomeruli to analogues. Our data suggest that activation of PKA-I or PKA-II might have an important role in the regulation of glomerular contractility.
van Bemmelen
M X P
MX
Institute of Pharmacology and Toxicology, Lausanne University, Switzerland.
Szczepańska-Konkel
M
M
Jastorff
B
B
Jankowski
M
M
Angielski
S
S
D000818:Animals; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007444:Inulin / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007444:Inulin; D000242:Cyclic AMP