Agonist-induced desensitization of beta-adrenoceptor function in humans. Subtype-selective reduction in beta 1- or beta 2-adrenoceptor-mediated physiological effects by xamoterol or procaterol.
We investigated the effects of beta 2- (procaterol 2 x 50 micrograms/day for 9 days) and beta 1- (xamoterol 2 x 200 mg/day for 14 days) adrenoceptor agonists on lymphocyte beta 2-adrenoceptor density and beta 1- and beta 2-adrenoceptor in vivo function (assessed as isoprenaline-infusion-evoked hemodynamic effects and exercise-induced tachycardia) in healthy volunteers. Procaterol decreased lymphocyte beta 2-adrenoceptor density and all beta 2-adrenoceptor-mediated in vivo effects but did not affect beta 1-adrenoceptor-mediated in vivo effects. In contrast, xamoterol neither affected lymphocyte beta 2-adrenoceptors nor beta 2-adrenoceptor-mediated in vivo effects but decreased beta 1-adrenoceptor-mediated in vivo effects. It is concluded that in humans, generally long-term application of beta 1- or beta 2-adrenoceptor agonists causes desensitization of beta-adrenoceptor function but in a beta-adrenoceptor subtype-selective fashion.
Brodde
O E
OE
Biochemical Research Lab, University of Essen, FRG.
Daul
A
A
Michel-Reher
M
M
Boomsma
F
F
Man in 't Veld
A J
AJ
Schlieper
P
P
Michel
M C
MC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D017265:Procaterol; D011412:Propanolamines / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D013618:Tachyphylaxis; D013997:Time Factors; D017307:Xamoterol
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D017307:Xamoterol; D007545:Isoproterenol; D017265:Procaterol