Histamine stimulates cAMP generating system in chick pineal gland.

Histamine stimulates cAMP generating system in chick pineal gland J.Z. Nowak and B. Sgk Department o f Biogenic Amines, Polish Academy o f Sciences, P-225,90-950 t b d i , Poland INTRODUCTION AND METHODS. The pineal gland is the major organ for melatonin (MEL) production both in mammals and lower vertebrates, including birds. MEL biosynthesis shows a circadian rhythmicity: the hormone levels, and activities o f a penultimate and key regulatory MEL biosynthetic enzyme serotonin N-acetyltransferase (NAT) , are respectively high and low during the nightldark and dayllight phase o f any daily 1ight:dark illumination cycle ( 1 ) . MEL biosynthesis is regulated by CAMP which stimulates the process o f NAT induction (1) . The mechanisms governing the circadian nature o f the activity o f both CAMPand MEL-generating systems in the chick pineal gland are not recognized in detail. It is known that procedures that in vitro and in vivo enhance the pineal CAMP content lead to increases in NAT activity and MEL release (1). On the other hand, exposure o f pinealocytes in culture or living animals to light at night rapidly decreases CAMP concentrations, NAT activity, and MEL levels (1). The aim o f the present work was to study i f histamine (HA), which is known to stimulate adenylate cyclase activity in many tissues o f different species (2 ) , including the chick retina and brain (3) , is able to affect CAMP generating system in the chick pineal. Experiments were performed on pineal glands excised from 12-16-day-old male white Leghorn chicks (maintained from the day o f hatching under 12h light: 12h dark (LD) lighting schedule, with lights on between 23:00 and 11:00) at the end o f the light phase. CAMP formation in isolated pineals, and the effect o f H A upon, was studied in the glands prelabelled with [3~]-adenine (NEN; spec.act. 27 Cilmmol), using the method o f Salomon et al. (4) . The results are expressed as the 3 percentage o f total tritium present as [ HI-CAMP in tissue (% conversion). RESULTS AND DISCUSSION. HA (0.1-1,000 yM) added to the incubation medium potently stimulated both basal and 1 yM forskolin-driven CAMP formation in a concentration-dependent manner, with an EC50 value o f 6-10 pM, reaching maximal effect at 100 yM (Fig. 1). The action o f H A was counteracted by selective HA H-2 receptor antagonists tiotidine (0.1-1 yM) and cimetidine (1-10 pM), and reduced by a selective HA H-1 receptor antagonist mepyramine ( 1 p M ) T o our knowledge, this is the first demonstration showing that HA, acting through H-2 type o f HA receptors (the role o f H-1 receptors in this HA action is not evident, and requires more study) stimulates CAMP formation in the vertebrate pineal gland. Further experiment? are now in progress to establish whether this HA potency i\ linked to MEL biosynthesis.