Enhanced expression of Giα protein and adenylyl cyclase signaling in aortas from 1 kidney 1 clip hypertensive ratsThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.

We have previously shown the augmented levels of Giα-2 and Giα-3 proteins (isoforms of inhibitory guanine nucleotide regulatory protein (G-protein)), and not of Gsα, in the hearts and aortas of spontaneously and experimentally induced hypertensive rats. The increased expression of Giα and blood pressure was restored toward WKY levels by captopril treatment, suggesting a role for angiotensin (Ang) II in the enhanced expression of Giα protein and blood pressure. This study was undertaken to investigate whether 1 kidney 1 clip (1K-1C) hypertensive rats that exhibit enhanced levels of Ang II also express enhanced levels of Giα proteins. Aortas from 1K-1C hypertensive rats were used. The expression of G-proteins was determined at protein levels with immunoblotting techniques, using specific antibodies for different isoforms of G-proteins. The levels of Giα-2 and Giα-3 proteins were significantly higher in aortas from 1K-1C hypertensive rats than in control rats; Gsα levels were unchanged. The inhibitory effect of low concentrations of guanosine 5′-[γ-thio]triphosphate (GTPγS) on forskolin (FSK)-stimulated adenylyl cyclase (AC) activity was significantly enhanced in aortas from 1K-1C hypertensive rats; the inhibitory effect of C-ANP4–23, which specifically interacts with the atrial natriuretic peptide (ANP)-C receptor, and Ang II on AC was attenuated. GTPγS, isoproterenol, glucagon, NaF, and FSK stimulated the AC activity in aortas from control and hypertensive rats to varying degrees; however, the stimulations were significantly lower in hypertensive rats than in control rats. These data suggest that aortas from 1K-1C hypertensive rats exhibit enhanced expression of Giα proteins and associated functions.

Functional and molecular aspects of renal prostaglandin receptors.

The diverse intrarenal effects of the prostaglandins (PG) are mediated by distinct guanine nucleotide regulatory protein (G-protein)-coupled receptors. The cDNA for these receptors have been cloned, their signal transduction mechanisms determined, and their intrarenal distribution mapped. PGE2, the major intrarenal prostaglandin, interacts with at least three distinct E-prostanoid (EP) receptors that are highly expressed in specific regions of the kidney. Each EP receptor not only selectively binds PGE2, but also preferentially couples to different signal transduction pathways, including: stimulation of cAMP generation, via Gq (EP2 and EP4 receptors); inhibition of cAMP generation, via Gi (EP3 receptors); and activation of phosphatidylinositol hydrolysis (EP1 receptor), via one of the Gq family members. Activation of each these EP receptors is responsible for a distinct renal effect of PGE2, including its well-described renal hemodynamic and transport effects along the nephron. Other intrarenal prostanoid receptors include the PGF2 alpha receptor (FP), the thromboxane A2 receptor (TP) and the prostacyclin receptor (IP). Knowledge about localization of these receptors and their affinities for receptor-selective agonists and antagonists should aid in the understanding of renal disease and the development of therapeutic strategies for the use of these prostaglandin analogs in select renal diseases.