EFFECTS OF MU-AGONISTS, DELTA-AGONISTS AND KAPPA-AGONISTS ON ISOLATEDRIGHT 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 maxi mal 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-50,48 8H 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 no t 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 presen ce of propranolol was 100 +/- 0 significantly (p < 0.01) higher than t hat obtained with U-50,488H alone. These results demonstrated that the depressant action of U-50,488H was not blocked in the presence of opi oid receptor antagonists and probably does not involve opioid receptor s. Furthermore, propranolol caused a dose-dependent potentiation of th e effects of the kappa-agonist supporting the conclusion that it is no t mediated by opioid receptors.