Role of G Proteins in the Regulation of the Cardiovascular System

Abstract

A precise description of the involvement of G proteins in regulation of the cardiovascular system is not possible at the present time although it is clear that they do have important regulatory roles. The cardiovascular system is composed of a variety of cell types, which are subject to control by several different hormones, as well as by hormones that have several different effects in the same cell type. Although, historically, variations in the type and number of receptors located on each cell have been used to explain this diversity of hormonal responses, we must now consider the large number and diversity of G proteins in any effort to understand the coordinated hormonal regulation of cellular functions. Given that there are eight known G proteins and several others have been speculated, each of which is composed of three subunits, each of which has several different forms, the possible combinations of subunits into functionally distinct G proteins is enormous. To place this newly described family of G proteins into the appropriate hormone signaling pathways will require a continued research effort. However, with recent progress in producing specific antibodies to each of the G protein subunits, it may now be possible to determine the specific receptor-effector functions of each G protein and their individual subunits.

Cardiac α1‐adrenoceptors stimulate a high‐affinity GTPase activity in sarcolemmal membranes from rabbit atrial and ventricular myocytes

“…This suggestion is supported by radioligand-binding studies performed with isolated intact rat ventricular myocytes which indeed indicate a lower number of a,-adrenoceptors (Buxton and Brunton, 1986) compared withmAChR (Buxton et al, 1985). In addition, the enzyme kinetics (i.e., binding and/or catalysis of GTP) of the a,-adrenoceptor-associated G-protein may be considerably different (i.e., slower) than the kinetics described for the cardiac mAChR-associated G-protein, G, (Robishaw and Foster, 1989;Schimerlik, 1989). In support of this, recent studies have described the purification of novel pertussis-toxin-insensitive Ga subunits which appear to have lower rates of GTPase activity (Casey et al, 1990) (Pang and Sternweis, 1990).…”

On the role of G protein activation and phosphorylation in desensitization to acetylcholine in guinea‐pig atrial cells.

“…5 suggests that direct activation of GK resulted in desensitization, it is possible that the desensitization was the result of another action of GTPyS, perhaps the formation of ATPyS from GTPyS by a transphosphorylation reaction; later it is shown that ATPyS eliminates 'K ACh-Therefore, the effect of activation of GK by AIF4-has also been investigated. It is well known that AlF4-activates G proteins, including Gi (GK is possibly Gi2 or Gi3, Robishaw & Foster, 1989) (Sternweis & Gilman, 1982;Gilman, 1984a, b; see also Blackmore & Exton, 1986;Magnu'sson, Halldorsson, Kjeld & Thorgeirsson, 1989;Woods, Dixon, Cuthbertson & Cobbold, 1990). AlF4-is able to activate G proteins by substituting for the y-phosphate of GTP -there are structural similarities between AlF4-and phosphate (Bigay, Deterre, Pfister & Chabre, 1985).…”

Signal transduction by G proteins in cardiac tissues.

“…Much progress has been made; ,B-adrenergic receptors,5-9 muscarinic cholinergic receptors,10 13 adenylate cyclase,14-18 and multiple G proteins19, 20 have been purified, cloned, and functionally characterized to varying degrees. As the details of molecular structure and function have been revealed for the adenylate cyclase system, it has been realized that G proteins do not represent an isolated signaling system.…”