Altered alpha 1-adrenoceptor binding in intact and adrenalectomized obese Zucker rats (fa/fa).
While many autonomic and metabolic defects associated with genetic obesity in the Zucker rat are corrected by adrenalectomy (Adx), brain adrenoceptor function has not been examined in this context. Here, 3 weeks after Adx or sham surgery, brains of 11 weeks old lean (Fa/Fa) and obese (fa/fa) male Zucker rats were assayed for alpha 1-([3H]prazosin; [3H]PRZ) and alpha 2-adrenoceptor ([3H]paraminoclonidine; [3H]PAC) binding by autoradiography. By genotype, obese rats had 19-256% higher [3H]PRZ binding than lean rats in the amygdala (central [ACN], basolateral [ABL], basomedial [ABM] and medial [MAN] nuclei [n.]), hypothalamus (dorsomedial n. [DMN] and lateral [LH]) and somatosensory cortex. In the ABL and ACN, increased maximal binding (Bmax) in obese rats was associated with decreased affinity (increased Kd). Three weeks after surgery, sham-operated obese rats gained 27% more weight than lean rats but lean and obese Adx rats gained the same amount of weight. Adx reduced [3H]PRZ binding in both lean and obese rats by 37-70% in the amygdala (ABM, ACN, MAN) compared to sham-operated rats. But, Adx selectively reduced [3H]PRZ binding only in lean rats in the ABL, DMN, ventromedial hypothalamic n. (VMN) and ventroposteromedial thalamic n. In most areas, decreases in maximal binding (Bmax) associated with Adx were accompanied by decreases in Kd. Unlike [3H]PRZ binding, there was no consistent genotype difference in [3H]PAC binding although Adx was followed by increased binding in obese and decreased binding in lean rats in the ABL. In only the VMN, obese rats had a 21% higher alpha 2- to alpha 1-adrenoceptor ratio than lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurology Service, Department of Veterans Affairs Medical Center, E. Orange, NJ 07018.
B E
BE
Levin
B
B
Planas
V H
VH
Routh
J
J
Hamilton
J S
JS
Stern
B A
BA
Horwitz
D000273:Adipose Tissue / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D001345:Autoradiography; D001835:Body Weight; D001923:Brain Chemistry / Q000502:physiology; D005838:Genotype; D008297:Male; D009765:Obesity / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D011224:Prazosin