Up- and down-regulation of central postsynaptic α₂ receptors reflected in the growth hormone response to clonidine in reserpine-pretreated rats

Abstract

The α-adrenergic mechanisms exert a stimulatory influence on the secretion of growth hormone (GH) in the rat. In the present study the α receptors involved in GH regulation were characterized with respect to subtype. It was also investigated whether the GH response to α receptor agonists can be utilized to assess changes in the responsiveness of central α receptors. The experiments were performed on rats with implanted intra-aortic cannulae allowing frequent blood sampling from freely moving animals. Plasma GH was determined by radioimmunoassay. Reserpine (10 mg/kg) caused a suppression of the normal pulsatile secretory pattern of GH. The α receptor agonist clonidine (CLON) given to reserpine-pretreated animals induced a dose-dependent increase in plasma GH. The effect of CLON (0.2 mg/kg) was prevented by pretreatment with the α₂ receptor antagonist yohimbine (3 mg/kg), but not by the α₁ receptor antagonist phenoxybenzamine (10 mg/kg). Chronic pretreatment with CLON or imipramine, either of which can be expected to produce a reduced sensitivity of central α₂ receptors, resulted in reduced GH responses to CLON. On the other hand, chronic treatment with yohimbine, which should cause denervation supersensitivity of α₂ receptors, led to enhanced GH responses to CLON. The results indicate that GH release in the rat is stimulated by postsynaptic α₂ receptors. They also suggest that the GH response to CLON can be used as a valid in vivo model reflecting decreased, as well as increased responsiveness of this type of receptor.