Contribution of Ca++ and calmodulin to the action of norepinephrine on renal prostaglandin synthesis and vascular tone.
We have investigated the contribution of Ca++ and calmodulin to the action of norepinephrine (NE) on prostaglandin (PG) synthesis and vascular tone in the Tyrode's perfused rat kidney. Lowering the Ca++ concentration (0.6 mM) reduced and raising the Ca++ concentration (5.4 mM) enhanced the renal vasoconstriction and PG output elicited by NE. Calcium channel blockers diltiazem or nimodipine inhibited the vasoconstriction and PG output caused by NE. Ca++-free Tyrode's solution containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid abolished NE-induced vasoconstriction and reduced PG output by 25 to 38%. Addition of intracellular Ca++ antagonists 8-(diethylamino) octyl 3,4,5 trimethoxybenzoate, dantrolene or ryanodine to Ca++-free Tyrode's solution inhibited NE-induced PG output. Calmodulin inhibitors trifluoperazine, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide or calmidazolium diminished PG output and the renal vasoconstriction elicited by NE in the presence and absence of Ca++. Mepacrine and indomethacin inhibited NE-induced renal vasoconstriction and PG output. Arachidonic acid-induced PG output was abolished by indomethacin but was unaltered by mepacrine, Ca++ antagonists or calmodulin inhibitors. We conclude that NE produces renal vasoconstriction by a mechanism that depends primarily on extracellular Ca++ and calmodulin, whereas NE-induced PG output depends on both extra- and intracellular Ca++ and calmodulin.
Cooper
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Malik
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D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011796:Quinacrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002147:Calmodulin; D011453:Prostaglandins; D014268:Trifluoperazine; D016718:Arachidonic Acid; D011796:Quinacrine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin; D007213:Indomethacin