Effects of kappa-opioid receptor agonists on stimulated phosphoinositide hydrolysis in rat kidney.
To determine the effects of kappa-opioid receptor agonists on phosphoinositide metabolism in rat renal cortex, tissue slices labelled with [3H]inositol were stimulated with norepinephrine or carbachol alone or in combination with the kappa-opioid receptor agonists, ethylketocyclazocine, trans-3,4-dichloro-N-methyl-N-[2-(pyrrolindinyl)-cyclohexyl)- benzeneacetamide (U50,488) and nalorphine. Both norepinephrine and carbachol stimulated phosphoinositide hydrolysis (measured in a LiCl buffer) concentration- and time-dependently. The EC50 and maximal stimulation of phosphoinositide hydrolysis for norepinephrine and carbachol were approximately 3 microM and 0.15 dpm released/dpm incorporated, respectively. Concentrations up to 1 mM of ethylketocyclazocine, U50,488 or nalorphine alone did not affect phosphoinositide hydrolysis. However, ethylketocyclazocine and U50,488 decreased 10 microM norepinephrine-stimulated phosphonositide hydrolysis concentration-dependently, each with an approximate IC50 of 30 microM. In contrast, nalorphine had no effect on norepinephrine-stimulated phosphoinositide hydrolysis. In addition, concentrations of up to 1 mM ethylketocyclazocine or U50,488 did not alter carbachol-stimulated phosphoinositide hydrolysis. The inhibitory effect of U50,488 and ethylketocyclazocine on norepinephrine-stimulated phosphoinositide hydrolysis was blocked by the selective kappa-opioid receptor antagonist, nor-binaltorphimine. These results indicate that kappa 1-opioid receptor stimulation may affect phosphoinositide metabolism in rat renal cortex by modulating the subcellular effects of renal alpha 1-adrenoceptor activation.
Mosaddeghi
M
M
Department of Pharmacology, Louisiana State University Medical Center, New Orleans 70112, USA.
Kapusta
D R
DR
Minor
L D
LD
Duan
N
N
Paul
D
D
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D016314:Ethylketocyclazocine / Q000494:pharmacology; D006868:Hydrolysis; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists; D013268:Stimulation, Chemical
D010716:Phosphatidylinositols; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D016314:Ethylketocyclazocine; D009271:Naltrexone; D002217:Carbachol; D009638:Norepinephrine