Beta-adrenoceptor expression on circulating mononuclear cells of idiopathic Parkinson's disease and autonomic failure patients before and after reduction of central sympathetic outflow by clonidine.
There is a short-term up-regulation of beta-adrenoceptors on peripheral blood mononuclear cells (PBMC) after reduction of central sympathetic outflow by clonidine in normal individuals. We have studied beta-adrenoceptor number and affinity on PBMC in idiopathic Parkinson's disease (PD), pure autonomic failure (PAF), and multiple system atrophy (MSA; Shy-Drager syndrome) patients and age- and sex-matched normal controls (NC) before and after intravenous administration of clonidine, an alpha 2-adrenoceptor agonist which lowers blood pressure predominantly by reducing CNS sympathetic outflow. Basal beta-adrenoceptor density was high in PAF but within the normal range in PD and MSA patients. After clonidine there was a decrease in plasma levels of noradrenaline (NA) and adrenaline (Ad) in PD, MSA, and NC, and an increase in growth hormone (GH) in PD, PAF, and NC. NC. In PAF, NA and Ad remained unchanged. In MSA, there was no increase in GH levels. There was an up-regulation of beta-adrenoceptors on PBMC at 30 and 60 minutes after clonidine administration, which returned to baseline values after 2 hours, and the affinity of the receptors was decreased in NC and PD patients. Intracellular production of cAMP after isoproterenol stimulation demonstrated that the up-regulation was not functional. Up-regulation after clonidine did not occur in PAF and MSA patients. The observed correlation of plasma NA and sympathetic defect with basal and clonidine-induced up-regulation of beta-adrenoceptors on PBMC may provide insight into beta-adrenoceptor changes in other tissues and also help in differentiating subgroups of autonomic failure patients.
Zoukos
Y
Y
Department of Neurochemistry, National Hospital for Neurology and Neurosurgery, London, UK.
Thomaides
T
T
Pavitt
D V
DV
Cuzner
M L
ML
Mathias
C J
CJ
D000328:Adult; D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000503:physiopathology*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D012016:Reference Values; D012791:Shy-Drager Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D003000:Clonidine