Effects of almitrine on the release of catecholamines from the rabbit carotid body in vitro.
1. Almitrine increases ventilation by stimulating the carotid body (CB) arterial chemoreceptors but neither its intraglomic target nor its mechanism of action have been elucidated. 2. We have tested the hypothesis that chemoreceptor cells are targets for almitrine by studying its effects on the release of 3H-catecholamines in an in vitro rabbit CB preparation. 3. It was found that almitrine (0.3 and 1.5 x 10(-6) M; i.e. 0.2 and 1 mg ml-1) increases the resting release of 3H-catecholamines from CBs (previously loaded with [3H]-tyrosine) incubated in a balanced 95% O2/5% CO2-equilibrated solution. 4. Almitrine at a concentration of 3 x 10(-6) M (2 mg l-1) also augmented the release of 3H-catecholamines elicited by incubating the CBs in a hypoxic solution (equilibrated with 7% O2/5% CO2 in N2), by high external K+ (35 mM) and by veratridine (2 x 10(-5) M), but did not modify release induced by dinitrophenol (7.5 x 10(-5) M). 5. At the same concentration (3 x 10(-6) M), almitrine increased the rate of dopamine synthesis and was ineffective in modifying the cyclic AMP levels in either normoxic or hypoxic CBs. 6. It is concluded that chemoreceptor cells are the intraglomic targets for almitrine. The mechanisms of action of almitrine on chemoreceptor cells are discussed.
Almaraz
L
L
Departamento de Bioquimica y Biologia Molecular y Fisiologia, Facultad de Medicina, Universidad de Valladolid, Spain.
Rigual
R
R
Obeso
A
A
Evrard
Y
Y
Gonzalez
C
C
D015765:Almitrine / Q000494:pharmacology*; D000818:Animals; D002344:Carotid Body / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism*; D066298:In Vitro Techniques; D008293:Malates / Q000494:pharmacology; D011817:Rabbits; D014316:Tritium
D002395:Catecholamines; D008293:Malates; D014316:Tritium; C030298:malic acid; D015765:Almitrine