Effects of Antagonists on Putative Histamine Receptors in the First Visual Neuropile of the Housefly (Musca Domestica)

Abstract

Intracellular recordings were made from the large monopolar cells (LMCs), which are the cells postsynaptic to photoreceptors, in the housefly Musca domestica. A multi-barrelled ionophoretic pipette glued to the recording electrode was used to apply a variety of cholinergic and histaminergic antagonists onto the recorded neurones. All substances which blocked the physiological response to light also antagonized the response to ionophoretically applied histamine, supporting the hypothesis that histamine is the neurotransmitter released by insect photoreceptors. In order of potency, the following drugs were found to block or reduce the LMCs responses to light: benzoquinonium ≥ gallamine > ranitidine ≥ atropine ≊ cimetidine > metiamide≊SK&F93479 ≥ mepyramine. Mecamylamine, scopolamine, dexetimide, nicotine, mequitazine, chlorpheniramine and clemastine were ineffective. Two other cholinergic ligands, hexamethonium and decamethonium, were much more potent than even benzoquinonium, but had the effect of facilitating and greatly slowing down the responses to light. Responses evoked by acetylcholine showed a different pharmacology, being blocked by mecamylamine but unaffected by hexamethonium. Despite testing a number of known cholinergic and histaminergic agents, no effective agonist for histamine was found. The results indicate the existence of a novel class of histamine-sensitive receptor with nicotinic features. In addition the unusual effects of a traditional HI agonist, 2-thiazolylethylamine, suggested the presence of a second, distinct class of histamine receptor.