Atrial natriuretic polypeptide secretion via selective activation of kappa-opioid receptor: role of dynorphin.
The present study was designed to investigate the direct effect of dynorphin on atrial natriuretic polypeptide (ANP) secretion in cultured rat atrial cardiocytes via a kappa-opioid receptor activation as well as the involvement of adenosine 3',5'-cyclic monophosphate (cAMP) system in the secretion of ANP from cardiocytes. Dynorphin stimulated ANP secretion dose and time dependently from 2-day cultured atrial cardiocytes. The dynorphin-induced ANP secretion was partially antagonized by MR2266, a selective kappa-opioid receptor antagonist. U-62066E, a selective kappa-opioid receptor agonist, stimulated ANP secretion. This stimulation was also antagonized by MR2266. However, no stimulation of ANP secretion was seen with [D-Ala2,D-Leu5]enkephalin, methionine (Met)-enkephalin, or [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin. Dynorphin at 10(-6) M significantly decreased the production of cAMP in the cultured cardiocytes. However, 10(-6) M Met-enkephalin had no effect on cAMP at all. The decrease in cAMP production by the addition of dynorphin was partially antagonized with a simultaneous addition of MR2266. The dynorphin-induced ANP secretion, as well as the basal secretion, were significantly decreased by the addition of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor, as compared with the respective controls. Dibutyryl cAMP at 10(-3) M significantly decreased the basal secretion of ANP as compared with the control. Therefore, the present studies show that dynorphin selectively stimulates ANP secretion, at least in part, via the activation of a specific kappa-opioid receptor.
Yamada
K
K
Division of Clinical Research and Internal Medicine, Sakura National Hospital, Chiba, Japan.
Yoshida
S
S
Shimada
Y
Y
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001575:Benzomorphans / Q000494:pharmacology; D002478:Cells, Cultured; D004232:Diuretics / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D007700:Kinetics; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017473:Receptors, Opioid, kappa
D001575:Benzomorphans; D004232:Diuretics; D004745:Enkephalins; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C027247:MR 2266; D004744:Enkephalin, Methionine; D016308:Enkephalin, Leucine-2-Alanine; D004399:Dynorphins; D009320:Atrial Natriuretic Factor; C051272:spiradoline; D015056:1-Methyl-3-isobutylxanthine