Subtype-selective modulation of human beta 1- and beta 2-adrenoceptor function by beta-adrenoceptor agonists and antagonists.
In healthy volunteers a 14-day treatment with the selective beta 1-adrenoceptor agonist xamoterol (2 x 200 mg/day) desensitized beta 1-adrenoceptor-mediated physiological effects, but did not affect beta 2-adrenoceptor-mediated effects; in contrast, a 9-day treatment with the selective beta 2-adrenoceptor agonist procaterol (2 x 50 micrograms/day) desensitized beta 1-adrenoceptor-mediated physiological effects, but did not affect beta 1-adrenoceptor-mediated effects suggesting that in general in man long-term treatment with beta-adrenoceptor agonists down-regulates beta-adrenoceptors, but in a beta-adrenoceptor subtype-selective manner. Similarly, in patients undergoing coronary artery bypass grafting chronic treatment with different beta-adrenoceptor antagonists without intrinsic sympathomimetic activity subtype-selectively up-regulated beta-adrenoceptors: non-selective antagonists (propranolol, sotalol) increased both cardiac beta 1- and cardiac, saphenous vein and lymphocyte beta 2-adrenoceptors, whereas beta 1-selective antagonists (metoprolol, atenolol, bisoprolol) increased only cardiac beta 1-, but not cardiac, saphenous vein or lymphocyte beta 2-adrenoceptors. Such a subtype-selective modulation of human beta 1- and beta 2-adrenoceptors should be taken into consideration when treating patients chronically with beta-adrenoceptor agonists and/or antagonists.
Brodde
O E
OE
Abteilung Nieren- und Hochdruckkrankheiten, Universität Essen, FRG.
Daul
A
A
Michel
M C
MC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta