Regulation of adrenergic receptor number following chronic noradrenaline infusion in the rabbit.
In order to study noradrenaline-induced regulation of alpha- and beta-adrenoceptors, groups of male New Zealand White rabbits (n = 8) were treated with intravenous noradrenaline (0.09 mumol/kg x h) or ascorbate (0.1%) for 10 days via osmotic minipumps implanted in the femoral vein, and the number of cardiac, lung and lymphocyte beta-adrenoceptors as well as renal and platelet alpha 2-adrenoceptors were determined. 1. The mean arterial blood pressure, heart rate and catecholamine levels were measured before commencing, and after 24 h and 10 days infusion. Circulating noradrenaline concentrations were elevated approximately 6-fold at 24 h and were sustained at these levels after 10 days administration of noradrenaline. There were no significant alterations in the blood pressure while a significant decrease in the heart rate was observed at 24 h. 2. Alpha 2-adrenoceptor density was assessed using [3H]-yohimbine. A significant decrease in the number of alpha 2-adrenoceptors in the kidney was observed following the 10 days infusion with noradrenaline. This down-regulation was in marked contrast to the lack of alteration in platelet alpha 2-adrenoceptor number and the platelet alpha 2-adrenoceptor mediated aggregatory response. 3. The density of beta-adrenoceptors in lymphocytes, heart and lung were quantified using (-)[125I]iodocyanopindolol (ICYP). The noradrenaline infusions caused significant reductions in beta-adrenoceptor number in the heart and lung (containing predominantly beta 1-adrenoceptors) but not in lymphocytes (possessing mainly beta 2-adrenoceptors). The KD-values (pM) for ICYP binding to heart and lung were also significantly decreased in the present studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Deighton
N M
NM
University Department of Materia Medica, Stobhill General Hospital, Glasgow, United Kingdom.
Brown
A D
AD
Hamilton
C A
CA
Reid
J L
JL
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D011941:Receptors, Adrenergic; D009638:Norepinephrine