Effect of Histamine on Gene Expression and Release of Proopiomelanocortin-Derived Peptides from the Anterior and Intermediate Pituitary Lobes in Conscious Male Rats

Abstract

Via activation of H₁ or H₂ receptors histamine (HA) stimulates the secretion of proopiomelanocortin (POMC)-derived peptides from the anterior (AL) and intermediate (IL) pituitary lobes of male rats. During selective inhibition of the AL or IL by pretreatment with dexamethasone (Dx) or bromocriptine (Br), respectively, we studied the effect of equipotent doses of intracerebroventricularly infused HA, the H₁-receptor agonist 2-thiazolylethylamine (2TEA) or the H₂-receptor agonist 4-methylHA (4MeHA) on the release of ACTH, β-endor-phin (β-END) immunoreactivity (ir) and α-melanocyte-stimulating hormone (α-MSH) in conscious male rats. Dx blocked the ACTH responses whereas Br prevented the α-MSH responses. Dx and Br equally inhibited the response of β-ENDir to HA and 4MeHA (80 and 70%, respectively). In contrast, the β-ENDir response to 2TEA was totally blocked by Dx but only inhibited 50% by Br. The inhibitory effect of Dx on the β-ENDir response to 2TEA was significantly stronger than the effect on the responses to HA and 4MeHA. POMC mRNA in the AL but not in the IL was increased almost 45% by HA and 2TEA and 20% by 4MeHA. Since all three histaminergic compounds in the doses used stimulated the release of β-ENDir equipotently, the results indicate that H₁-receptor activation predominantly affects the release and synthesis of β-ENDir from the AL while H₁-receptor activation affects the release of β-ENDir equally from the two lobes and only to some extent increases the synthesis in the AL. Thus, the findings suggest a differential involvement of H₁ and H₂ receptors in the mediation of the HA-induced effect on POMC-derived peptides in the AL and IL.