Indirect evidence for a role of prostaglandins as second messengers of the prejunctional effect of opioids in guinea-pig ventricular preparations.

The cardiac response to adrenergic nerve stimulation was dose dependently reduced in a statistically significant manner by 1-10 microM dynorphin-(1-13) in isolated atria, and by 0.1-1 microM dynorphin-(1-13) in guinea-pig ventricular preparations. The inhibitory effect of dynorphin was maintained in atria that had been pretreated with two cyclooxygenase inhibitors at concentrations that induce an 80% inhibition of the enzyme, namely indomethacin 3 microM and acetylsalicylic acid 200 microM. The inhibitory effect of dynorphin disappeared in similarly pretreated ventricular preparations. These results suggest that, whilst the mediation of the effect of dynorphin is carried out mainly by specific opioid receptors in the atrial section, in the ventricular tissue it occurs through the endogenous prostanoid system.