INHIBITION OF [H-3] CATECHOLAMINE RELEASE AND CA2-BODY CHEMORECEPTOR CELLS( CURRENTS BY PROSTAGLANDIN E(2) IN RABBIT CAROTID)

1. Basal release of [H-3]catecholamine ([H-3]CB) from rabbit carotid b odies (CBs), previously incubated in the presence of [3H]tyrosine, was not significantly modified by prostaglandin E(2) (PGE(2)). On the con trary, PGE(2) (3-300 nM) produced a dose-dependent inhibition of the l ow P-o2-evoked release of [H-3]CB. The inhibition was greatest (55%) a t a low intensity of hypoxic stimulation (incubating solution P-o2 app roximate to 66 mmHg) and decreased with increasing intensities of hypo xia. Chronic denervation of the CB did not modify the response to PGE( 2). 2. The release of [3H]CA induced by incubating the CBs in a hyperc apnic-acidic solution (P-co2 approximate to 132mmHg; pH=6.60) and by d initrophenol (100 mu M) was not significantly modified by 300 nM PGE(2 ). 3. PGE(2) (300 nM) inhibited the release of [H-3]CA elicited by inc ubating the CBs in a high K+ (35 mM)-containing solution. The release response elicited by high K+ (25 mM) was strongly augmented by a dihyd ropyridine agonist of Ca2+ channels, Bay K 8844, at a concentration of 1 mu M. The Bay K 8644 effect was partly inhibited by PGE(2) (300 nM) . 4. Using whole-cell recordings in freshly dispersed or short-term cu ltured chemoreceptor cells from adult rabbits it was found that Ca2+ c urrents (I-ca) were reversibly inhibited by bath application of PGE(2) . A good parallelism exits between the dose-response curves for PGE(2) inhibition of I-ca in isolated chemoreceptor cells and high extracell ular [K+]- or hypoxia-evoked release of [H-3]CA from the whole CB. 5. When recordings were made with an internal solution lacking GTP and co ntaining 100 mu M GDP-beta-S, a GDP analogue which inhibits G-protein cycling, PGE(2) did not inhibit I-Ca in chemoreceptor cells. 6. These results indicate that PGE(2) inhibits the release of [H-3]CA induced b y hypoxic and high extracellular [K+] stimulation in adult CB chemorec eptor cells by reducing the entry of Ca2+ through voltage-dependent Ca 2+ channels. This effect of the prostanoid on the Ca2+ channels appear s to be mediated by a G protein-dependent mechanism.