BINDING AND ELECTROPHYSIOLOGY OF THE MUSC ARINIC ANTAGONIST QNB IN MAMMALIAN RETINA

Purpose Based upon the extensive information from various laboratories on cholinergic enzymes and receptors in mammalian retina as well as c holinergic effects on retinal neurons we became interested in studying (1) retinal binding of a muscarinic antagonist, Quinuclidinyl benzila te (QNB) and (2), effects of the antagonist on retinal information pro cessing. Methods Eyes from deeply anesthetized cats were used for homo genate of freshly isolated retina in the binding study, or they were a rterially perfused for electrophysiology in vitro. The electroretinogr am (ERG) and the compound action potential of the optic nerve (optic n erve response, ONR) were recorded under rod- and cone-stimulating cond itions. QNB was infused intraarterially for 10-30 min, followed by was hout (avoiding recycling or extraocular metabolism). Results H-3-QNB r evealed a high affinity to muscarinic receptors with a dissociation co nstant K-D of 0.27 nM and a relatively high density of muscarinic bind ing sites of 110 fmol per mg protein. - QNB enhanced the amplitude of the ERG b-wave, but decreased dose-dependently and reversibly the comp onents of the ONR. In addition, we observed a moderate vasoconstrictio n as indicated by a slight, dose-related decrease in now rate of perfu sion. Conclusion The biochemical data on binding of H-3-QNB in connect ion with the marked electrophysiolgical changes induced by QNB suggest a substantial contribution of muscarinic cholinergic transmission in the cat retina.