Up-regulation of beta-adrenoceptors on circulating mononuclear cells after reduction of central sympathetic outflow by clonidine in normal subjects.
Short term regulation of beta-adrenoceptors in peripheral blood mononuclear cells after sympathetic activation has been previously documented in normal individuals but changes after a central reduction in sympathetic activity are not known. We have studied beta-adrenoceptor number and affinity on peripheral blood mononuclear cells in normal subjects, before and after intravenous clonidine, an alpha 2-adrenoceptor agonist which lowers blood pressure predominantly by reducing central nervous system sympathetic outflow. After clonidine there was a decrease in plasma levels of noradrenaline and adrenaline, and an increase in growth hormone. There was up-regulation of beta-adrenergic receptors on peripheral blood mononuclear cells 30 and 60 min after clonidine which was related to the fall in blood pressure, noradrenaline and adrenaline levels and to the increase in growth hormone levels. The affinity of the receptors was decreased. Return to baseline values was observed after 2 h. Intracellular production of cAMP after isoproterenol stimulation demonstrated that the up-regulation was not functional. Our studies indicate short term up-regulation of beta-adrenoceptors in peripheral blood mononuclear cells after clonidine. These observations after a reduction in sympathetic activity may be of importance if they mirror the pattern of redistribution of adrenoceptors, which are present in a wide range of tissues.
Zoukos
Y
Y
Department of Neurochemistry, Multiple Sclerosis Society Laboratory, London, UK.
Thomaides
T
T
Pavitt
D V
DV
Leonard
J P
JP
Cuzner
M L
ML
Mathias
C J
CJ
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004298:Dopamine / Q000097:blood; D004837:Epinephrine / Q000097:blood; D013006:Growth Hormone / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D013006:Growth Hormone; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine