Bindung und Elektrophysiologie des muskarinischen Antagonisten QNB in der Säugetiernetzhaut

Abstract

Based upon the extensive information from various laboratories on cholinergic enzymes and receptors in mammalian retina as well as cholinergic effects on retinal neurons we became interested in studying (1) retinal binding of a muscarinic antagonist, Quinuclidinyl benzilate (QNB) and (2), effects of the antagonist on retinal information processing. Eyes from deeply anesthetized cats were used for homogenate of freshly isolated retina in the binding study, or they were arterially perfused for electrophysiology in vitro. The electroretinogram (ERG) and the compound action potential of the optic nerve (optic nerve response, ONR) were recorded under rod- and cone-stimulating conditions. QNB was infused intraarterially for 10-30 min, followed by washout (avoiding recycling or extraocular metabolism). 3H-QNB revealed a high affinity to muscarinic receptors with a dissociation constant KD of 0.27 nM and a relatively high density of muscarinic binding sites of 110 fmol per mg protein. QNB enhanced the amplitude of the ERG b-wave, but decreased dose-dependently and reversibly the components of the ONR. In addition, we observed a moderate vasoconstriction as indicated by a slight, dose-related decrease in flow rate of perfusion. The biochemical data on binding of 3H-QNB in connection with the marked electrophysiological changes induced by QNB suggest a substantial contribution of muscarinic cholinergic transmission in the cat retina.