Involvement of Alpha-Adrenergic Mechanisms in Growth Hormone Release Induced by Opioid Peptides in Conscious Rats

Abstract

The effects of synthetic enkephalin analog (FK 33–824) and β-endorphin on growth hormone (GH) secretion and their interaction with brain monoamines were investigated in unanesthetized male rats. Blood samples (0.4 ml each) were withdrawn every 10–20 min for 6 h from a catheter chronically implanted in the right atrium. In all control rats, immunoreactive GH secretion was pulsatile in nature and two major GH bursts were found to occur around 12.00 and 15.30.The opioid peptides were injected between bursts at 14.00. Following an intravenous administration of FK 33–824 (10 μg/100 g b.w.), there was an abrupt increase in plasma GH, which was significantly suppressed by naloxone (125 μg/ 100 g b.w., i.v.), a specific opiate antagonist. Pretreatment with reserpine (1 mg/100 g b.w., i.p.) abolished not only the natural GH burst but also the GH response to FK 33–824. Pretreatment with dopamine-β-hydroxylase inhibitors, diethyldithiocarbamate (DDC, 100 mg/100 g b.w., i.v.) and fusarate (10 mg/100 g b.w., i.v.) also inhibited the natural GH burst and GH rise induced by FK 33–824. Intravenous injection of clonidine (15 μg/100 g b.w.), an α-adrenergic stimulant, resulted in an increase in plasma GH in the rats pretreated with reserpine, DDC or fusarate. Phenoxybenzamine (1 mg/100g b.w., i.v.), an α-adrenergic blocking agent, inhibited the GH response to FK 33–824. On the other hand, GH release induced by FK 33–824 was not influenced by propranolol (1 mg/100 g b.w., i.v.), a β-adrenergic blocking agent, nor pimozide (0.1 mg/100g b.w., i.v.), a dopamine antagonist. Intraventricular administration of β-endorphin (5 μg/rat) also increased the plasma GH levels which were lowered by phenoxybenzamine. These findings suggest that α-adrenergic mechanisms are involved in GH release induced by opioid peptides in the rat.