Agonist-induced desensitization of dopamine D-1 receptors in bovine retina and rat striatum.
We have investigated agonist-induced desensitization of dopamine (DA) D-1 receptor mediated accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) in bovine retinas and rat striata in vitro. Tissues were exposed to various pharmacological agents for 60 min, washed and homogenized. D-1 agonist-promoted accumulation of cAMP in the presence of adenosine 5'-triphosphate (ATP) and 5'-guanylylimidodiphosphate (GppNHp) was then measured. Retinas and striata incubated with DA or (+) SKF 38393 (100 microM each) displayed diminished capacities to accumulate cAMP when they were re-exposed to the same drugs. As expected, retinas and striata treated wtih (+) SKF 38393 also showed an attenuated formation of cAMP when restimulated with DA. In addition, D-1 receptors in retinas that had been treated with quinpirole, a D-2 agonist, did not become desensitized. Furthermore, 0.2 microM SCH 23390 prevented D-1 receptor subsensitivity caused by 100 microM DA. Interestingly, retinas and striata incubated with forskolin, a direct stimulator of adenylyl cyclase, also displayed a diminished enzymatic response to restimulation by the same agent, as well as by DA. Additionally, retinas incubated with 100 microM DA were refractory to forskolin-induced cAMP formation. Finally, results of 3H-SCH 23390 binding to control and DA-treated retinas indicated that agonist treatment did not induce significant changes in either receptor density or binding affinity. The data indicate that bovine retinas and striatal slices in vitro are suitable to investigate various aspects of the desensitization of neuronal responses to DA D-1 agonists or forskolin.
Department of Pharmacology, University Medical Center, Geneva, Switzerland.
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Bugnon
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Schorderet
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D000242:Cyclic AMP / Q000096:biosynthesis; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D012680:Sensitivity and Specificity; D013268:Stimulation, Chemical
D017447:Receptors, Dopamine D1; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases