Different effects of metoclopramide and domperidone on GH release in type I male diabetics

Dopamine (DA) has a physiological role in the control of GH release from the pituitary. Studies have been carried out using DA agonist or antagonist, since in normal subjects DA does not cross the blood-brain-barrier (BBB). In contrast, the BBB is altered in type I diabetics, who respond to DA with a significant increase of GH release. In these patients Metoclopramide (MCP), an antidopaminergic drug, is also capable of stimulating GH release. In a previous paper, we suggested that this effect could be related to enhanced blood concentrations of DA, due to a reduced peripheral DA catabolism determined by MCP. However, since MCP crosses the BBB, an effect of this drug on other hypothalamic neurotransmitters could not be excluded. The purpose of the present study was to determine whether Domperidone (DOM) a drug which does not cross the BBB, but as well as MCP is thought to increase blood levels of DA, is also capable of inducing GH release in diabetics. Sixteen type I male diabetics were injected intravenously with MCP (6) or DOM (10) and a week later with normal saline. Ten normal subjects participated as controls to all three tests. MCP and DOM did not produce any effects in the normal controls; as expected, MCP induced a marked increase in serum levels of GH in the diabetics, while in contrast DOM did not stimulate GH secretion in diabetics. These data suggest that the effect of MCP is not due to the dopaminergic pathway previously described, but rather to a modulation of some other neurotransmitter at hypothalamic level, or to a direct effect on the pituitary in diabetics.