Histamine in Macaca mulatto monkey cardiac sympathetic nerve system: A morphological and functional assessment

Our previous study demonstrated the co-localization of histamine with norepinephrine (NE) within superior cervical ganglia (SCG), and the release of histamine from sympathetic nerve endings of guinea pig evoked by stimulations. We have now further investigated that whether the histamine can be synthesized, stored and released from the sympathetic nerve systems of Macaca mulatto monkey, and investigated the modulation of the sympathetic endogenous histamine release through histamine H3 receptor in the monkey cardiac sympathetic nerve system. Double-labeled immunofluorescence technique was applied to investigate co-localization of histamine and NE in SCG of Macaca mulatto monkey. The cardiac sympathetic nerve terminals (synaptosomes) of Macaca mulatto monkey was prepared and depolarized with 50 mmol/L K+. Histamine released from synaptosomes was detected by spectrofluorometer and regulations of histamine release through Ca2+, Ca2+-channel blockers, H3-receptor agonist (R)-α-methylhistamine and histamine H3-receptor antagonist, thioperamide were observed. Co-localization of histamine and NE was identified within the same neuron of SCG. Release of histamine was Ca2+-dependent and inhibited by N-type Ca2+-channel blocker ω-conotoxin, but not affected by the L-type Ca2+-channel blocker lacidipine. Compound 48/80, a mast cell releaser, did not affect cardiac synaptosome histamine exocytosis. Cardiac synaptosome histamine release was augmented by the enhanced synthesis of histamine or the inhibition of histamine metabolism. Histamine H3-receptor activation by (R)-α-methylhistamine inhibited high K+-evoked histamine release and thioperamide blocked the effects of (R)-α-methylhistamine. These results firstly showed that histamine co-existed with NE within sympathetic neurons of monkey and the exocytosis of histamine from sympathetic terminals could be regulated by presynaptic histamine H3 receptors. Sympathetic histamine may act as a neurotransmitter to modulate sympathetic neurotransmission.