DOXAPRAM STIMULATES DOPAMINE RELEASE FROM THE INTACT RAT CAROTID-BODYIN-VITRO

Hypoxic chemotransduction by the carotid body is believed to involve i nhibition of K+ channels in type I cells, leading to depolarization an d the opening of Ca2+ channels which triggers catecholamine release. W e have investigated whether the clinically used ventilatory stimulant doxapram (which, like hypoxia, blocks K+ channels in isolated type I c ells) also stimulates catecholamine release from the intact carotid bo dy in vitro, by pre-incubating tissues with [H-3]tyrosine. H-3 overflo w was evoked by raised extracellular [K+] (60 mM) and by cyanide (2 mM ). Doxapram (15-150 mu M) also evoked H-3 overflow in a concentration dependent manner; and doxapram-evoked release was inhibited by the Ca2 + channel blocker nifedipine (5 mu M). Analysis of released tritiated compounds suggested that doxapram preferentially stimulated the releas e of dopamine. Our results indicate that the mechanism of action of do xapram shares similarities with that of hypoxia in the carotid body.