title: Doxapram stimulates dopamine release from the intact rat carotid body in vitro.
abstract: Hypoxic chemotransduction by the carotid body is believed to involve inhibition of K+ channels in type I cells, leading to depolarization and the opening of Ca2+ channels which triggers catecholamine release. We have investigated whether the clinically used ventilatory stimulant doxapram (which, like hypoxia, blocks K+ channels in isolated type I cells) also stimulates catecholamine release from the intact carotid body in vitro, by pre-incubating tissues with [3H]tyrosine. 3H overflow was evoked by raised extracellular [K+] (60 mM) and by cyanide (2 mM). Doxapram (15-150 microM) also evoked 3H overflow in a concentration dependent manner, and doxapram-evoked release was inhibited by the Ca2+ channel blocker nifedipine (5 microM). Analysis of released tritiated compounds suggested that doxapram preferentially stimulated the release of dopamine. Our results indicate that the mechanism of action of doxapram shares similarities with that of hypoxia in the carotid body.
authors.affiliation: Department of Pharmacology, Leeds University, UK.
authors.forename: R
authors.initials: R
authors.lastname: Anderson-Beck
authors.forename: L
authors.initials: L
authors.lastname: Wilson
authors.forename: S
authors.initials: S
authors.lastname: Brazier
authors.forename: I E
authors.initials: IE
authors.lastname: Hughes
authors.forename: C
authors.initials: C
authors.lastname: Peers
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004315:Doxapram / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
chemical_list: D004315:Doxapram; D009543:Nifedipine; D011188:Potassium; D004298:Dopamine