On the mechanism of relaxin action: the involvement of adenylyl cyclase signalling system

Abstract

The molecular mechanism of relaxin action was studied taking into account the evolutionary relationship of the peptides belonging to the insulin superfamily and using the authors' previous data [1, 2]on the involvement of the adenylyl cyclase (AC) signalling system in the action of insulin and related peptides. Human relaxin 2 (10 −12–10 −8 M) has been shown to cause a dose-dependent activating effect on AC in the human myometrium (+370%), in rat skeletal muscles (+117%) and the smooth foot muscles of the bivalve mollusc Anodonta cygnea (+73%). In these tissues mammalian insulin and insulin-like growth factor-1 (IGF-1) also had the AC activating effect. The order of efficiency of the above peptides based upon their ability to induce the maximal AC activating effect was as follows: relaxin>IGF-1>insulin (human myometrium); IGF-1>relaxin>insulin (rat skeletal muscle); molluscan insulin-like peptide>IGF-1>insulin>relaxin (molluscan muscle). The relaxin AC activating effect was inhibited with a selective tyrosine kinase blocker tyrphostin 47 and potentiated with Gpp[NH]p providing evidence for the participation of the receptor-tyrosine kinase and G-protein of the stimulatory type (G s) in the regulatory action of relaxin. The conclusion is that the signalling chain: receptor tyrosine kinase⇒G s protein⇒AC is involved in the mechanism of relaxin action.