cyclic-gmp and 4-methylhistamine

Histamine and 4-methylhistamine inhibited ganglionic transmission in the rat superior cervical ganglion in vitro via H2-histaminergic receptors. Under blockade of H2-receptors, 4-methylhistamine sometimes showed slight facilitation of ganglionic transmission, when repetitive stimuli were applied. The H1-receptor agonist, 2-pyridylethylamine, was ineffective. Histamine and 4-methylhistamine increased both cyclic AMP (cAMP) and cyclic GMP (cGMP) levels in concentrations depressing ganglionic transmission, whereas 2-pyridylethylamine increased only cAMP concentrations in the isolated ganglia. Histamine-induced accumulation of cyclic nucleotides was only partially prevented by either histamine--H1- and H2-receptor antagonists, but abolished by their combination. It is concluded that changes in intraganglionic cyclic nucleotides induced by histaminergic receptor agonists did not apparently correlate with their effect on ganglionic transmission in vitro.

Topics: Action Potentials; Animals; Cyclic AMP; Cyclic GMP; Ganglia, Sympathetic; Histamine; Histamine H1 Antagonists; Histamine H2 Antagonists; In Vitro Techniques; Male; Methylhistamines; Pyridines; Rats; Rats, Inbred Strains; Synaptic Transmission

We have investigated the effect of histamine on pig epidermal cell outgrowths in vitro. Histamine inhibited the epidermal cell outgrowths (and also mitosis). This inhibition was partially counteracted by a specific H2 antagonist, cimetidine. Inhibition was maximal at a histamine concentration of 10(-4) M and was less at 10(-3) M. These histamine concentrations respectively coincide with the optimal concentrations for accumulating intracellular cyclic AMP (via H2 receptors) and cyclic GMP (via H1 receptors) in the same pig epidermal slice system. 4-Methyl-histamine, a pure H2 agonist, which only increased the intracellular cyclic AMP level but not the cyclic GMP level, caused a maximal outgrowth inhibition at 10(-3) M. Attempts to counteract the histamine effects due to cyclic GMP accumulation by various H1 antagonists (so that 10(-3) M histamine would have caused maximal outgrowth inhibition) were unsuccessful, since the addition of each H1 antagonist alone strongly inhibited the outgrowth. These data strongly suggest a dual role of histamine through the cyclic nucleotide system; i.e., histamine inhibits epidermal cell growth by elevating the intracellular cyclic AMP level via an H2 receptor, while histamine at high concentrations (10(-3) M) partially counteracts the inhibition by increasing cyclic GMP via an H1 receptor.

Topics: Animals; Cells, Cultured; Cimetidine; Cyclic AMP; Cyclic GMP; Epidermis; Epinephrine; Histamine; Histamine H1 Antagonists; Methylhistamines; Swine