Cannabinoid CB1 receptors and ligands in vertebrate retina: Localization and function of an endogenous signaling system

CB1, a cannabinoid receptor enriched in neuronal tissue, was found in high concentration in retinas of rhesus monkey, mouse, rat, chick, goldfish. and tiger salamander by using a subtype-specific polyclonal antibody. Immunola beling was detected in the two synaptic layers of the retina, the inner and outer plexiform layers, of all six species examined. In the outer plexifor m layer. CB1 was located in and/or on cone pedicles and rod spherules. Labe ling was detected in some amacrine cells of all species and in the ganglion cells and ganglion cell axons of all species except fish. In addition. spa rse labeling was found in the inner and/or outer segments of the photorecep tors of monkey, mouse, rat, and chick. Using GC/MS to detect possible endog enous cannabinoids. we found 3 nmol of 2-arachidonylglycerol per g of tissu e. but no anandamide was detectable. Cannabinoid receptor agonists induced a dramatic reduction in the amplitude of voltage-gated L-type calcium chann el currents in identified retinal bipolar cells. The presence and distribut ion of the CB1 receptor. the large amounts of 2-arachidonylglycerol found, and the effects of cannabinoids on calcium channel activity in bipolar cell s suggest a substantive role for an endogenous cannabinoid signaling system in retinal physiology, and perhaps vision in general.