Histamine H3 receptors mediate inhibition of noradrenaline release from intestinal sympathetic nerves

Open Access
Publisher Website
Google Scholar
Abstract
The present study investigates whether presynaptic histamine receptors regulate noradrenaline release from intestinal sympathetic nerves. The experiments were performed on longitudinal muscle‐myenteric plexus preparations of guinea‐pig ileum, preincubated with [3H]‐noradrenaline. In the presence of rauwolscine, electrically‐induced [3H]‐noradrenaline release was inhibited by histamine or R‐α‐methylhistamine, whereas it was unaffected by pyridylethylamine, impromidine, pyrilamine, cimetidine, thioperamide or clobenpropit. The inhibitory effects of histamine or R‐α‐methylhistamine were antagonized by thioperamide or clobenpropit, but not by pyrilamine or cimetidine. In the absence of rauwolscine, none of these drugs modified the release of [3H]‐noradrenaline. The modulatory action of histamine was attenuated by pertussis toxin and abolished by N‐ethylmaleimide. Tetraethylammonium or 4‐aminopyridine enhanced the evoked tritium outflow and counteracted the inhibitory effect of histamine. However, the blocking effects of tetraethylammonium and 4‐aminopyridine were no longer evident when their enhancing actions were compensated by reduction of Ca2+ concentration in the superfusion medium. Histamine‐induced inhibition of tritium output was enhanced by ω‐conotoxin or low Ca2+ concentration, whereas it was not modified by nifedipine, forskolin, rolipram, phorbol myristate acetate, H7 or lavendustin A. The present results indicate that presynaptic H3 receptors, located on sympathetic nerve endings, mediate an inhibitory control on intestinal noradrenergic neurotransmission. It is suggested that these receptors are coupled to Gi/Go proteins which modulate the activity of N‐type Ca2+ channels through a direct link, thus reducing the availability of extracellular Ca2+ at the level of noradrenergic nerve terminals. British Journal of Pharmacology (2000) 129, 1387–1396; doi:10.1038/sj.bjp.0703194