Receptors coupled to adenylate cyclase in isolated rabbit retina.
Intact pieces or homogenates of rabbit retina were exposed to various established or putative retinal neurotransmitters for the study of receptors (or receptor-subtypes) linked to the production of cAMP. Since a dopamine-sensitive adenylate cyclase has been previously characterized in the retina of several species, the novel D(1)-agonist SKF 38393 was applied under similar experimental conditions. This compound was found to be more potent (although less efficacious) than dopamine, confirming the existence of a population of D(1)-receptors. On the other hand, the novel D(1)-antagonist SCH 23390 was able to inhibit the stimulating effects of dopamine and of SKF 38393 in a concentration-dependent manner. Attempts to detect D(2)-receptors (negatively coupled with adenylate cyclase) were not conclusive, when a selective D(2)-agonist (quinpirole) was applied in the absence or presence of a D(2)-antagonist (sulpiride). A stimulation of cAMP production (mediated by A(2)-receptors) was also detected in response to adenosine or adenosine-analogs, which was blocked by IBMX in a concentration-dependent manner. The effects of adenosine were potentiated in the presence of dipyridamole, an adenosine uptake inhibitor. Compared to the effects of dopamine and adenosine, the stimulation induced by VIP, a retinal neuropeptide, was found to be much more pronounced. These results indicate that retinal cAMP can be generated by three different neurotransmitters in an independent way via the stimulation of specific receptors.
Schorderet
M
M
Department of Pharmacology, University Medical Center (CMU), 1 rue Michel Servet, Geneva Switzerland; School of Pharmacy, University of Lausanne, Lausanne, Switzerland.