Denervation, supersensitivity and muscarinic receptors in the cat iris

An attempt was made to establish the molecular basis for denervation supersensitivity in the muscarinic system of the cat iris. Several components of that system, namely cholineacetyltransferase (CAT), acetylcholinesterase (AcChE) and the muscarinic acetylcholine receptor were determined following unilateral extirpation of the ciliary ganglion in cats that resulted in supersensitivity to pilocarpine. Marked decreases in CAT activity (80-90 per cent) as well in AcChE activity (25-60 per cent) were noted, starting on the 4th day following ciliary ganglionectomy. No change occurred in the concentration of the muscarinic receptors, nor in the dissociation constant of the muscarinic antagonist N-methyl-4-piperidyl benzilate (4-NMPB), on days 4, 7, and 14 following denervation. It is concluded that the development of denervation supersensitivity is not underlain by quantitative or qualitative changes in the muscarinic receptors. These and other results suggest, rather, that the mechanism responsible for parasympathetic denervation supersensitivity at the smooth muscle of the cat iris sphincter, must be connected with post-receptorial events.