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Adenylyl Cyclase Signaling Mechanism of Relaxin Action

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Abstract

In connection with our discovery of the adenylyl cyclase signaling mechanism (ACSM) of action of some peptides belonging to the insulin superfamily, a possibility of its involvement in action of another insulin superfamily peptide, relaxin, was studied. It was shown for the first time that human relaxin-2 (10−12–10−8 M) activated adenylyl cyclase (AC) in a dose-dependent manner. The maximal peptide effect was revealed at a concentration of 10−8 M. Under condition of the hormonal action the basal enzyme activity increased by +310% in human myometrium, by +117%, in rat skeletal muscles, and by +49%, in foot smooth muscles of the bivalve mollusc Anodonta cygnea. Insulin and mammalian insulin-like growth factor-I (IGF-I) also produced the AC activating effect in these muscles. The order of efficiency of these peptides, based on their ability to induce the maximal AC stimulating effect, was as follows: relaxin > IGF-I > insulin (human myometrium); IGF-I > relaxin > insulin (rat skeletal muscle); insulin-like peptide of Anodonta (ILPA) > IGF-I > insulin > relaxin (molluscan muscle). The relaxin activating effect on AC was potentiated by a guanine nucleotide, the non-hydrolyzed analog of GTP, guanylylimidodiphosphate (Gpp[NH]p), which indicates participation of Gs-protein in realization of this effect. This effect was inhibited by a tyrosine kinase selective blocker, tyrphostin 47, and a phosphatidylinositol-3-kinase (PI-3-K) selective blocker, wortmannin. Thus, for the first time, participation of ACSM in the relaxin action has been established. This mechanism, as suggested at the present time state of its study, includes the following signal pathway: receptor-tyrosine kinase ⇒ PI-3-K ⇒ Gs-protein ⇒ AC.

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Russia

    S. A. Plesneva, L. A. Kuznetsova, A. O. Shpakov & M. N. Pertseva

  2. Ott Institute of Obstetrics and Gynecology, Russian Academy of Medical Sciences, St. Petersburg, Russia

    E. V. Omel'yanyuk

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  1. S. A. Plesneva
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  2. L. A. Kuznetsova
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  4. A. O. Shpakov
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  5. M. N. Pertseva
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Plesneva, S.A., Kuznetsova, L.A., Omel'yanyuk, E.V. et al. Adenylyl Cyclase Signaling Mechanism of Relaxin Action. Journal of Evolutionary Biochemistry and Physiology 36, 734–743 (2000). https://doi.org/10.1023/A:1017578822254

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