Snake venom containing M5 muscarinic receptor activity inhibits carbachol‐induced pigment granule dispersion in retinal pigment epithelium isolated from bluegill sunfish.

Teleost pupils are of a fixed diameter so the adjustments necessary for optimal conditions for photoreceptor function involve several retinomotor movements. Among these is the migration of melanin pigment granules in the retinal pigment epithelium into apical projections in response to bright light conditions. Pigment granule migration reduces photobleaching of rod photoreceptors. Pigment granule movements occurs in response to neurochemicals secreted by the retina. Previous work has shown that acetylcholine is involved in inducing light‐adaptive pigment dispersion and that it acts through a muscarinic receptor to do so. Muscarinic receptors belong to the G‐protein coupled receptor superfamily, and five different muscarinic receptors have been molecularly cloned in human. Many pharmacological agents tested suggest that pigment granule movement is mediated by an M‐odd receptor, but so far the identity of that receptor has been elusive. To test whether the M5 muscarinic receptor pathway is involved in eliciting pigment granule dispersion, isolated retinal pigment epithelium from bluegill was subjected to treatment with the venom from Naja naja sputatrix. Extracts from this venom have been shown to inhibit M5 activity. We show here that treatment with 90 μg/ml crude snake venom inhibits pigment granule dispersion induced by treatment with the acetylcholine analog, carbachol. Further dose‐response characterization and competition assays are underway to rule out non‐muscarinic receptor‐mediated effects on pigment position.