Effects of the C-terminal peptide of the αs subunit of the G protein on the regulation of adenylyl cyclase and protein kinase A activities by biogenic amines and glucagon in mollusk and rat muscles

Abstract

The C-terminal parts of the a subunits of heteromeric G proteins play an important role in the functional linkage of G proteins with receptors of the serpentine type. The present report describes studies of the effects of the C-terminal octapeptide 387-394 of the alphaS subunit of the mammalian G protein on the transmission of the hormonal signal via the hormone-sensitive adenylyl cyclase signal system, whose major components are receptors of the serpentine type, G proteins, and the enzymes adenylyl cyclase and protein kinase A. The peptide synthesized here, 387-394 amide (10(-7) - 10(-4) M), dose-dependently decreased adenylyl cyclase and protein kinase A activities stimulated by serotonin and glucagon in smooth muscle from the freshwater bivalve mollusk Anodonta cygnea and by the beta agonist isoproterenol in rat skeletal muscle. At a concentration as low as 10(-7) M, the peptide released potentiation of the stimulatory effects of hormones on adenylyl cyclase activity due to the non-hydrolyzable guanine nucleotide analog Gpp[NH]p. At the same time, it had almost no effect on the stimulation of adenylyl cyclase activity by non-hormonal agents (NaF, Gpp[NH]p, and forskolin). The inhibitory effects of hormones on adenylyl cyclase and protein kinase A activities persisted in the presence of the peptide. Our data demonstrate the importance of the C-terminal part of the alphaS subunit of the stimulatory G protein for its functional linkage with receptors of the serpentine type and throw light on the molecular mechanisms of the interactions between G proteins and receptors.

Molecular mechanisms for the effect of mastoparan on G proteins in tissues of vertebrates and invertebrates

“…Basal level of GTP binding (rat myocardium, 2.37±0.14 pmol [8-3 H]-GppNHp per mg protein; rat brain striatum, 6 Table 1), while peptide 385-394 of G s protein α ssubunit did not modulate the effect of mastoparan in rat tissues, but slightly decreased it in mussel muscles. C-terminal peptides selectively and competitively impair signal transduction via G proteins from which they are derived [4,10,14]. The stimulatory effect of peptides I and II on GTP binding was sensitive to the presence of both C-terminal peptides.…”

Changed sensitivity of adenylate cyclase signaling system to biogenic amines and peptide hormones in tissues of starving rats

“…Activity of AC was measured as follows [11]: fractions of plasma membranes were incubated in a reaction mixture at 37 o C for 10 min and AC acti- Fig. 1.…”

Effect of Stimulators upon Human Hepatic Adenylate Cyclase Activity: A Tool of Nitroimidazole Cytotoxicity Assessment

“…Activation and attenuation of adenylate cyclase due to GTP binding protein as messenger in membrane receptor-cyclase binding was reviewed (Van Dyke 2004; Kimura, Nakane, and Nagata 1987). Guanine nucleotides have been shown to be required for adenylate cyclase stimulation by hormones and drugs (Skurat et al 1985;Sanchez-Yague et al 1994;Shpakov et al 2005). The present study extended the information that human hepatocytes have specific receptors for GITP, GTP and Kupffer cells have receptors for prostaglandin E 2 and F 2 .…”