Studies on Adrenocorticotropic Hormone Receptor Using Isolated Rat Adrenocortical Cells

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To clarify the function of ACTH receptors, the actions of ACTH on cyclic AMP formation, Ca2+-influx across cell membrane, and corticoidogenesis were examined using dispersed adrenocortical cells prepared from the rat adrenal gland. 1) There are two types of ACTH receptors from Scatchard analysis of 125I-ACTH1-24 binding to the cell, the one receptor is of high affinity and low capacity (dissociation constant (Kd1)=2.6×10-10M and 7, 350 sites per cell), and the other one is of low affinity and high capacity (dissociation constant (Kd2)=7.1×10-9M and 57, 400 sites per cell). 2) Both apparent dissociation constants derived from the effects of ACTH on corticoidogenesis and Ca2+-influx well correspond with Kd1 of the high affinity receptor. 3) Apparent dissociation constant obtained from the effect of ACTH on cyclic AMP formation is in good agreement with Kd2 of the low affinity receptor. Thus it could be deduced from these data that the high affinity receptor is concerned with an increased Ca2+-influx to regulate corticoidogenesis at physiological levels of ACTH, whereas the low affinity receptor is coupled to adenylate cyclase at supraphysiological concentrations of ACTH.
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