REGULATION OF HORMONE-RESPONSIVE ADENYLATE CYCLASE

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1. Muscarinic receptors have been classified into M1- and M2- subtypes based on their affinity for the antagonist pirenzepine. We now show that both NG108-15 and SK-N-SH cells have M2 receptors. Yet, in the former cells, the receptors are coupled only to inhibition of adenylate cyclase; and in the latter cells, to stimulation of phosphoinositide breakdown. Thus, the same muscarinic receptor subtype can couple to two different signal transduction systems. 2. We have succeeded in solubilizing the D- 1 dopamine receptor from rat striatal membranes and reconstituting it into phospholipid vesicles. The receptor remains functional and couples to G proteins as measured by agonist high affinity state is increased over 6-fold from that in the original membranes. This may have important implications for the physiological state of the D-1 receptor in striatal membranes and its ability to mediate dopaminergic responses. 3. The hydrodynamic properties of the gonadotropin receptor from MLTC-1 cells has been determined. These cells contain gonadotropin receptors coupled to adenylate cyclase. Under nondenaturing conditions, the Mr of the receptor is 130 kDa compared to 80 kDa under denaturing conditions. Thus, the receptor may be composed of hormone-binding and non-binding subunits. Following desensitization of the cells by choriogonadotropin, the hydrodynamic properties of the receptor changes; the receptor binds less detergent and exhibits a more elongated frictional ratio but retains the same Mr. Thus, desensitization appears to involve a physical change in the gonadotropin receptor which may promote its uncoupling from adenylate cyclase.