Regulation by histamine of cyclic nucleotide levels in sympathetic ganglia.
An investigation has been carried out of the role of histamine H1- and H2-receptors in the control of cyclic guanosine 3':5'-monophosphate (cGMP) and cyclic adenosine 3':5'-monophosphate (cAMP) levels in blocks of bovine superior cervical ganglion. The data suggest that activation of H1-receptors is associated with cGMP accumulation and that activation of H2-receptors is associated with cGMP accumulation. Histamine increased both cGMP and cGMP levels with similar time course and concentration-response relationships. Low concentrations of the H1-receptor agonist 2-(2-aminoethyl)thiazole increased cGMP but not cAMP levels. Conversely low concentrations of the H2-receptor agonist 4-methylhistamine increased cAMP but not cGMP levels. H1-receptor antagonists blocked the histamine-induced increase in cGMP at low concentrations but blocked the cAMP increase only at substantially higher concentrations. Conversely, H2-receptor antagonists blocked the histamine-induced increased in cAMP but not cGMP. The effects of histamine on cyclic nucleotide levels did not appear to be mediated via the release of an endogenous neurotransmitter. The histamine-induced increase in cGMP appeared to be mediated through calcium: the increase in cGMP required the presence of calcium in the extracellular medium, and the calcium ionophore A23187 caused a calcium-dependent increase in cGMP. When considered with previous electrophysiological and biochemical findings in sympathetic ganglia, a correspondence can be seen: both histamine (at H1-receptors) and acetylcholine (at muscarinic receptors) raise cGMP levels and are associated with excitatory actions; both histamine (at H2- receptors) and dopamine raise cAMP levels and are associated with inhibitory actions.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002417:Cattle; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009711:Nucleotides / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000187:drug effects
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D009711:Nucleotides; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D002118:Calcium