ANTAGONISM OF MUSCARINIC RECEPTORS IN THE RABBIT IRIS-CILIARY BODY BY8-OH-DPAT AND OTHER 5-HT1A RECEPTOR AGONISTS

Physiological studies have shown that serotonin and 5-HT1A agonists ca n influence muscarinic function in the rabbit iris-ciliary body (ICE). The purpose of this study was to examine whether a direct interaction exists between muscarinic and 5-HT1A receptors in the ICE. At high co ncentrations, the 5-HT1A agonist 8-OH-DPAT attenuated the carbachol-in duced stimulation of inositol phosphates (InsPs) production, but this was not blocked by the presence of 5-HT1A antagonists. In contrast, se rotonin failed to influence carbachol-induced InsPs formation. Moreove r, 8-OH-DPAT but not serotonin displayed affinity for [H-3]QNB binding sites in the ICE. The combined data suggest that activation of 5-HT1A receptors in the ICE does not cause a modulation of muscarinic recept or-stimulated phosphoinositide turnover. The data instead suggest that , at high concentrations, 8-OH-DPAT acts as an antagonist at muscarini c receptors and in this way influences muscarinic receptor function. T he mechanism of 5-HT-induced modulation of muscarinic function in the ICE therefore remains to be elucidated.