Effects on human lymphocyte transformation of drugs inhibiting lipoxygenase enzyme pathways of arachidonic acid metabolism

Abstract

Histamine-induced cyclic AMP (cAMP) accumulation was studied in purified primary cultures of type-1 and type-2 astrocytes from neonatal rat brain. Histamine induced remarkable cAMP accumulation in type-1 astrocytes in a dose-dependent manner (EC50 = 1.2 × 10−5 M, Emax = 1100% of control). In contrast, histamine had no significant effect on cAMP accumulation in type-2 astrocytes. Famotidine, an H2-antagonist, dose-dependently inhibited histamine-induced cAMP accumulation in type-1 astrocytes (Ki = 3 × 10−8 M), but mepyramine (10−6 M), an H1-antagonist, had no effect. Dimaprit and impromidine, H2-agonists, stimulated cAMP accumulation, but 2-pyridylethylamine, an H1-agonist, did not stimulate it nor augment the H2-agonist-induced cAMP accumulation. These results indicate that (1) histamine induces cAMP accumulation in type-1 astrocytes but not in type-2 astrocytes, and that (2) histamine-induced cAMP accumulation in type-1 astrocytes is mediated by H2-receptors without significant augmentation via H1-receptors.