Antagonism of muscarinic receptors in the rabbit iris-ciliary body by 8-OH-DPAT and other 5-HT1A receptor agonists.
Physiological studies have shown that serotonin and 5-HT1A agonists can influence muscarinic function in the rabbit iris-ciliary body (ICB). The purpose of this study was to examine whether a direct interaction exists between muscarinic and 5-HT1A receptors in the ICB. At high concentrations, the 5-HT1A agonist 8-OH-DPAT attenuated the carbachol-induced stimulation of inositol phosphates (InsPs) production, but this was not blocked by the presence of 5-HT1A antagonists. In contrast, serotonin failed to influence carbachol-induced InsPs formation. Moreover, 8-OH-DPAT but not serotonin displayed affinity for [3H]QNB binding sites in the ICB. The combined data suggest that activation of 5-HT1A receptors in the ICB does not cause a modulation of muscarinic receptor-stimulated phosphoinositide turnover. The data instead suggest that, at high concentrations, 8-OH-DPAT acts as an antagonist at muscarinic receptors and in this way influences muscarinic receptor function. The mechanism of 5-HT-induced modulation of muscarinic function in the ICB therefore remains to be elucidated.
Chidlow
G
G
Nuffield Laboratory of Ophthalmology, University of Oxford, United Kingdom.
Osborne
N N
NN
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018727:Muscarinic Antagonists; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin