Regulation of Norepinephrine Release from Isolated Bovine Irides by Histamine

Abstract

In the present study, we investigated the effect of histamine on sympathetic neurotransmission from isolated, superfused bovine irides. We also studied the pharmacology of prejunctional histamine receptors that regulate the release of norepinephrine (NE) from this tissue. The effect of exogenous histamine and various histamine receptor agonists was examined on the release of [(3)H]-norepinephrine ([(3)H]NE) triggered by electrical field stimulation using the Superfusion Method. Histamine receptor agonists caused a concentration-dependent inhibition of field-stimulated [(3)H]NE overflow with the following rank order of potency: imetit > histamine > R-alpha-methylhistamine. In all cases, the inhibitory action of histamine receptor agonists was attenuated at high concentrations of these compounds. The histamine receptor antagonists, clobenpropit (H(3)-antagonist/H(4)-agonist) and thioperamide (H(3)-antagonist) blocked the inhibitory response elicited by R-alpha-methylhistamine and imetit, respectively. Inhibitory effects of R-alpha-methylhistamine and clonidine were not additive suggesting that prejunctional H(3)- and alpha(2)-adrenoceptors coexist at neurotransmitter release sites. We conclude that histamine produces an inhibitory action on sympathetic neurotransmission in the bovine iris, an effect mimicked by selective H(3)-receptor agonists and blocked by H(3)-antagonists.