Isolated adrenal cortex cells: ACTH agonists, partial agonists, antagonists; cyclic AMP and corticosterone production |
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Authors: | S Seelig G Sayers |
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Affiliation: | Department of Physiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 U.S.A. |
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Abstract: | Isolated adrenal cortex cells respond to the addition of ACTH1–39 or analogs with increased production of cyclic AMP and corticosterone. It is estimated that cyclic AMP production need proceed at less than 20% of maximum to induce maximum corticosterone production. ACTH1–24, [Lys17, Lys18]ACTH1–8 amide, and ACTH1–16 amide induce a maximum rate of cyclic AMP and of corticosterone production equal to those of ACTH1–39. The relative potencies as determined by cyclic AMP and by corticosterone production are in excellent agreement. The analog, ACTH5–24, induces maximum cyclic AMP production equal to 45% of that of the natural hormone, but as predicted, induces maximum corticosterone production equal to that of ACTH1–39. The derivative, [Trp(Nps)9]ACTH1–39 induces 77% of maximum corticosterone production and less than 1% of maximum cyclic AMP production. The fragment ACTH11–24 is a competitive antagonist of ACTH1–39 for both cyclic AMP and corticosterone production. The observations on agonists, a partial agonist and a competitive antagonist are in harmony with the “second messenger” role assigned to cyclic AMP. A provisional model, based on the fit of the experimental observations to a set of equations, provides expressions of “intrinsic activity,” “receptor reserve”, “sensitivity”, and “amplification” in terms of maximum cyclic AMP production, concentration of ACTH which induces maximum cyclic AMP production and concentration of cyclic AMP which induces maximum corticosterone production. |
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