Copyright © 1998 by Institute of Pharmacology
Polish Academy of Sciences 		Pol. J. Pharmacol., 1998, 50, 307-314
ISSN 1230-6002
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EFFECTS OF CALCIUM IONS AND SUBSTANCES AFFECTING Ca2+-RELATED MECHANISMS ON HISTAMINE-EVOKED STIMULATION OF CYCLIC AMP FORMATION IN CHICK PINEAL GLAND
 Jolanta B. Zawilska1,2, Agata Woldan-Tambor1,2, Jerzy Z. Nowak1#
 1 Department of Biogenic Amines, Polish Academy of Sciences, POB-225, Tylna 3, PL-90-950 ŁódŸ, Poland,
2 Department of Pharmacology, Medical University of ŁódŸ, Muszyńskiego 1, PL 90-151 ŁódŸ, Poland

Effects of calcium ions and substances affecting Ca2+-related mechanisms on histamine-evoked stimulation of cyclic AMP formation in chick pineal gland. J.B. ZAWILSKA, A. WOLDAN-TAMBOR, J.Z. NOWAK. Pol. J. Pharmacol., 1998, 50, 307-314.

In avian central nervous system (CNS), and particularly in the pineal gland, histamine (HA) potently stimulates synthesis of cyclic AMP in intact tissue, and only weakly affects adenylyl cyclase activity in membrane preparation. In this work, we focussed on calcium (Ca2+) as a possible link in the mechanism through which HA affects cyclic AMP generation in the chick pineal. The problem was studied in two sets of experiments where the action of HA on the pineal cyclic AMP was tested: (1) in the incubation medium containing various compounds influencing Ca2+ influx and/or Ca2+ intracellular concentration /action (Ca2+-ionophore calcimycin, Ca2+-channel agonist Bay-K 8644, Ca2+-channels blockers: diltiazem, verapamil, nifedipine and w-conotoxin-GVIA, CaCl2, EGTA in the absence of CaCl2 in the incubation medium, as well as calmodulin inhibitors: calmidazolium and W-7), and (2) in a CaCl2-free incubation medium yet containing different concentrations of BaCl2, CdCl2, CoCl2, MgCl2, and NiSO4. The results of the first series were mostly negative; an exception was the inhibiton of the HA-evoked cyclic AMP formation observed in the presence of 5.2 and 10.4 mM CaCl2. In the second series of experiments, divalent cations (however with the exception of Mg2+, which was inactive at concentrations up to 15.6 mM) inhibited the HA-evoked cyclic AMP production, with the following rank order of potency: Cd2+ >> Co2+ >> Ni2+ > Ba2+. The inhibitory effect of CdCl2 was prevented by nifedipine. Taken together, the present data suggest that intracellular Ca2+-related mechanisms are not of major importance in the HA action on cyclic AMP synthesis in the chick pineal. It could be suspected that the inhibition of the HA-driven cyclic AMP formation by high concentrations of Ca2+, and other divalent cations, probably resulted from their direct inhibitory interaction with the catalytic site of the pineal adenylyl cyclase.

Key words: cyclic AMP, histamine, Ca2+, Ca2+-related mechanisms, divalent cations, pineal gland, chick
  # correspondence
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