Pertussis toxin-sensitive G protein modulates the ability of histamine to stimulate cAMP production in the chick pineal gland

Histamine (HA) is a potent stimulator of cAMP synthesis in various structures of chick brain, including the pineal gland. The action of HA is mediated by specific, membrane bound H(2)-like receptors, whose pharmacological profile is different from that described for H(2) receptors in mammalian tissues. In this work, we analyzed the effects of cholera toxin (CTX) and pertussis toxin (PTX), well-known modulators of G(s) and G(i)/G(o) protein, respectively, on the stimulatory action of HA on cAMP synthesis in the chick pineal gland organ cultures. HA and its two biologically active methylated derivatives, 2-methylHA and 4-methylHA, markedly increased cAMP content in the chick pineal glands. Pretreatment of the chick pineal glands with CTX potently stimulated basal cAMP production. In CTX-pretreated glands, elevations of cAMP synthesis evoked by HA, 2-methylHA and 4-methylHA were additive to those produced by CTX, which is an observation suggesting that H(2)-like HA receptors in the chicken pineal gland are not coupled to G(s) proteins. Pretreatment of the chick pineal glands with PTX significantly enhanced the stimulatory effect of HA and, to a greater extent, 2-methylHA on cAMP production. The enhancing action of PTX on the HA-evoked cAMP formation was not modified by mepyramine, a selective H(1)-type HA receptor antagonist. It is suggested that in the chick pineal gland, a population of HA receptors is coupled to G(i) (or G(o)) protein. Stimulation of these receptors would tonically suppress the activity of the cAMP generating system functionally linked to H(2)-like HA receptors.