Cyclic guanosine 3':5'-monophosphate mimics the effects of light on a circadian pacemaker in the eye of aplysia

Environmental light regulates the phase of a circadian oscillator in the eye of Aplysia. We are attempting to define the events involved in transmitting light information from the environment to the circadian pacemaking mechanism in the eye. In this paper, we present several lines of evidence that cyclic guanosine 3':5'-monophosphate (cGMP) is involved in the photic entrainment pathway. Light increases the level of cGMP in eyes without having detectable effects on cyclic adenosine 3':5' -monophosphate (cAMP). An analogue of cGMP, 8-bromoguanosine 3':5' -cyclic monophosphate (cGMP), can shift the phase of the circadian rhythm from the eye; the phase response curves for light and for 8-bromo cGMP are indistinguishable. Neither 8-bromo cAMP nor 8-bromo 5'-GMP mimics the effect of light or of 8-bromo cGMP on the rhythm. Light and 8-bromo cGMP appear to use convergent mechanisms for entrainment since the effects of these two treatments are nonadditive. Also, low Na⁺ solutions antagonize the effects of both treatments. Finally, the kinetics of phase shifting by 8-bromo cGMP are similar to the kinetics of phase shifting by light. In addition to perturbing the circadian rhythm, 8-bromo cGMP increases the frequency of spontaneous optic nerve impulses. The pattern of nerve impulses during 8-bromo cGMP treatment is the same as the pattern of impulses produced by light. The excitatory effect of 8-bromo cGMP, the lower Na⁺ blockade of the effects of 8-bromo cGMP, and the involvement of membrane depolarization in phase shifting by light suggest that depolarization mediates the effect of 8-bromo cGMP on the rhythm. The cellular site at which 8-bromo cGMP acts remains to be determined. However, 8-bromo cGMP does not appear to affect the rhythm by acting on R-type photoreceptors in the eye since 8-bromo cGMP had no effect on the membrane potential of these photoreceptors. At least two roles for cGMP are possible to explain our results. cGMP may be involved in transduction in non-R-type photoreceptors in the eye. Alternatively, cGMP may not be involved in transduction but may be elevated in cells as a result of the photoreceptor potential.