Prostaglandin-mediated inhibition of noradrenaline release: IV. Prostaglandin synthesis is stimulated by myocardial adrenoceptors differing from the alpha- and beta-type.

The release of prostaglandin E elicited by sympathomimetic amines was studied in the isolated rabbit heart. The hearts were prepared according to Langendorff, with conventional recording of stroke frequency and contractile force. Assays were made of the outflow of PGE during exposition to equimolar concentrations of methoxamine, noradrenaline, adrenaline and isoprenaline, in the absence and in the presence of phentolamine or propranolol. Noradrenaline caused an almost four-fold increase in the basal outflow of PGE from the heart, while methoxamine (an alpha-adrenoceptor agonist) and isoprenaline (a beta-adrenoceptor agonist) were both ineffective in this respect. Thus, the PGE-releasing capacity of the drugs was not correlated to their ability to activate alpha- or or beta-adrenoceptors. Furthermore, no relation was obtained between the PGE release induced by the drugs and the increase in heart rate and contractile force elicited by them. It is suggested that sympathomimetic drugs trigger PGE synthesis and release in the rabbit myocardium following activation of a hitherto unobserved adrenoceptive mechanism, optimally stimulated by NA.