Influence of brain histamine on growth hormone secretion induced by alpha-2-receptor activation

The effects of histamine (HA) and of (R) alpha-methyl-histamine (alpha-MeHA; a drug that decreases histaminergic tone through activation of presynaptic H3 receptors) on growth hormone (GH) secretion induced by clonidine (CLO), an alpha 2-adrenergic agonist, were examined in rats. HA (0.1 mumol/rat intracerebroventricularly) and alpha-MeHA (10 mg/kg i.a.) were administered 5 min and 3 h, respectively, before CLO (0.25 mg/kg i.a.). Blood samples for hormone determination were drawn from freely moving rats at various times before and after drug treatment. To characterize the mechanisms underlying the inhibition of GH secretion by HA, the effect of HA on GH induced by CLO was examined in rats depleted of catecholamine by pretreatment (2 h before) with alpha-methyl-p-tyrosine (alpha-MpT, 200 mg/kg s.c.) and in rats depleted of somatostatin by pretreatment (4 h before) with cysteamine (300 mg/kg s.c.). HA completely suppressed the GH-releasing effect of CLO whereas alpha-MeHA significantly enhanced the GH response to CLO. Neither alpha-MpT nor cysteamine pretreatment modified the inhibitory activity of HA on GH secretion elicited by CLO. The present results indicate that the inhibitory activity of brain HA on GH release consequent to activation of central alpha 2-receptors does not involve a modulatory action on catecholaminergic or somatostatinergic neurons but probably other mechanisms like the modulation of neurons synthetizing GH-releasing hormone.