Effects of mu-, delta- and kappa-agonists on isolated right atria of the rat.
The present study examined the effects of morphine, DAMGO, DPDPE and U-50, 488H on auricular rate on isolated right atria of the rat. All the opioid agonists tested induced a decrease of auricular rate. The maximal effect obtained with U-50,488H (75 +/- 8.3%) was significantly (p < 0.001) higher than that obtained with morphine (12 +/- 2.7%), DAMGO (8 +/- 0.6%) or DPDPE (11 +/- 1.8%). The inhibitory effects of U-50,488H were not antagonized by the presence of naloxone (10(-7) or 5 x 10(-7) M) or MR-2266 (10(-7) or 5 x 10 (-7) M). Moreover, U-50,488H did not change the auricular chronotropism in the presence of atropine (5 x 10(-7) M). In this case the maximal inhibitory effect was 79 +/- 6.7%, similar to that obtained with the kappa-agonist alone (75 +/- 8.3%). Propranolol (10(-8) or 5 x 10(-8) M) modified the inhibitory effect of U-50,488H. The maximal effect obtained by the kappa-agonist in presence of propranolol was 100 +/- 0 significantly (p < 0.01) higher than that obtained with U-50,488H alone. These results demonstrated that the depressant action of U-50,488H was not blocked in the presence of opioid receptor antagonists and probably does not involve opioid receptors. Furthermore, propranolol caused a dose-dependent potentiation of the effects of the kappa-agonist supporting the conclusion that it is not mediated by opioid receptors.
Micol
J A
JA
Department of Physiology and Pharmacology, Faculty of Medicine, University of Murcia, Spain.
Laorden
M L
ML
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001575:Benzomorphans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000819:agonists; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists
D001575:Benzomorphans; D004745:Enkephalins; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D001285:Atropine; D020881:Enkephalin, D-Penicillamine (2,5)-; D011433:Propranolol