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.