Up- and down- regulation of central postsynaptic alpha 2 receptors reflected in the growth hormone response to clonidine in reserpine-pretreated rats.
The alpha-adrenergic mechanisms exert a stimulatory influence on the secretion of growth hormone (GH) in the rat. In the present study the alpha receptors involved in GH regulation were characterized with respect to subtype. It was also investigated whether the GH response to alpha receptor agonists can be utilized to assess change in the responsiveness of central alpha 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 alpha 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 alpha 2 receptor antagonist yohimbine (3 mg/kg), but not by the alpha 1 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 alpha 2 receptors, resulted in reduced GH responses to CLON. On the other hand, chronic treatment with yohimbine, which should cause denervation supersensitivity of alpha 2 receptors, led to enhanced GH responses to CLON. The results indicate that GH release in the rat is stimulated by postsynaptic alpha 2 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.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D012110:Reserpine; D013006:Growth Hormone; D003000:Clonidine