Prostaglandin-mediated inhibition of noradrenaline release: III. Separation of prostaglandins released from stimulated hearts and analysis of their neurosecretion inhibitory capacity

Abstract

Isolated rabbit hearts were infused with 14C-arachidonic acid and subjected to sympathetic nerve stimulation. Prostaglandins in the cardiac effluent were extracted and separated using thin layer chromatography. Other hearts were infused with un-labelled arachidonic acid and the effluent was assayed for neurosecretion inhibitory capacity on the field-stimulated guinea pig vas deferens, and for anti-aggregatory activity on ADP-induced platelet aggregation. PGs in the effluent from hearts infused with un-labelled arachidonic acid were extracted and separated on TLC, and the different fractions were assayed for neurosecretion inhibitory activity. Sympathetic nerve stimulation after preincubation with 14C-AA elicited outflow of four different peaks of 14C-labelled PGs: one chromatographing close to PGF 2α (probably mainly 6-keto-PGF 1α), and three peaks corresponding to PGA 2/PGB 2, PGD 2, and PGE 2 respectively. The cardiac interstitial effluent contained anti-aggregatory material which was inactivated by heat treatment, and thus probably identical to PGI 2. The cardiac effluent also contained material with neuro-secretion inhibitory activity, which was resistant to heat treatment. Fractional assay of the TLC separated cardiac effluent demonstrated that the neurosecretion inhibitory activity chromatographed with PGE 2 only. It has earlier been observed that endogenous PGs inhibit trans-mitter release in sympathetically stimulated organs. On the basis of the current data we suggest that PGE 2 is the only physiological inhibitor of sympathetic transmitter release.