Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 8498529

Decrease in Gs protein expression may impair adenylate cyclase activation in old kidneys.

C T Liang·J Barnes·H Hanai·M A Levine
View original source ↗Export metadata ↓

Abstract

The possibility that alteration in stimulatory guanine nucleotide-binding protein (Gs) expression may contribute to the blunting of renal parathyroid hormone (PTH)-stimulated adenylate cyclase in aged rats was examined. Using rat cDNA probe, we identified a Gs alpha-subunit (Gs alpha) of 1.9 kb. Age did not alter the size of Gs alpha mRNA. The level of Gs alpha mRNA [normalized to poly(A)+ RNA] was decreased 23%, which was consistent with our previous report that Gs alpha protein decreased in senescence. In contrast, mRNA level of Gi alpha 2 increased with age. Level of beta-actin mRNA did not change with age. Nuclear runoff assay was performed to determine the transcription rate of Gs mRNA. Synthesis of poly(A)+ RNA and total RNA was reduced 39% and 37%, respectively, in nuclei prepared from old kidney, which suggested a general decline in RNA synthesis capacity in old rats. Our results also showed the transcription rate of Gs alpha mRNA in aged rats was reduced 89%, a decrease far exceeding that observed for total RNA or poly(A)+ RNA. We concluded that the decrease in steady-state level of Gs alpha mRNA was specific and probably was due to a reduction in the transcription activity. Thus alteration in Gs transcription may contribute, at least in part, to the impaired renal adenylate cyclase activation in aged rats.

Explore related subjects

Adenylyl CyclasesAgingAnimalsBlotting, NorthernEnzyme ActivationGTP-Binding ProteinsKidneyMaleRNA, MessengerRatsRats, WistarTranscription, GeneticJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

C T Liang, J Barnes, H Hanai, M A Levine. 1993. Decrease in Gs protein expression may impair adenylate cyclase activation in old kidneys.. https://doi.org/10.1152/ajprenal.1993.264.5.f770

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Evidence for multiple signaling pathways in single squid olfactory receptor neurons.

At least two different G-protein-mediated transduction cascades, the adenylate cyclase and phospholipase C (PLC) pathway, process chemosensory stimuli for various species. In squid olfactory receptor neurons (ORNs), physiological studies indicate that both pathways may be present; however, confirmation of the transduction molecules at the protein level is absent. Here we provide evidence that the G-proteins involved in both adenylate cyclase and PLC pathways are present in squid ORNs (Lolliguncula brevis). We used immunoblotting to show that Galpha(olf), Galpha(q), and a downstream effector, enzyme PLC140, are present in the squid olfactory epithelium (OE). To localize these proteins to one or more of the five morphological cell types described for squid OE, paraformaldehyde-fixed olfactory organs were cryosectioned (10 microm), double-labeled for Galpha(olf), Galpha(q), or PLC140, and imaged. Analysis of serial sections from entire olfactory organs for epithelial area and patterns of immunofluorescence revealed a region of highest immunoreactivity at the anterior half of the organ. At the cellular level, type 1 cells could not be distinguished morphologically and were not included in the analysis. The three labeling patterns observed in type 2 cells were Galpha(q) alone, PLC140 alone, and colocalization of Galpha(q) and PLC140. Subsets of cell types 3, 4, and 5 showed colocalization of Galpha(olf) with Galpha(q) but not with PLC140. These data suggest that the PLC pathway predominates in type 2 cells; however, coexpression of Galpha(olf) with Galpha(q) in cell types 3, 4, and 5 suggests that both pathways may participate in olfactory transduction in non-type 2 squid ORNs.

Adenylyl Cyclases↗
PubMed2007

Chronic but not acute intracerebroventricular administration of amyloid beta-peptide(25-35) decreases somatostatin content, adenylate cyclase activity, somatostatin-induced inhibition of adenylate cyclase activity, and adenylate cyclase I levels in the rat hippocampus.

Although alterations in adenylate cyclase (AC) activity and somatostatin (SRIF) receptor density have been reported in Alzheimer's disease, the effects of amyloid beta-peptide (Abeta) on these parameters in the hippocampus are unknown. Our aim was to investigate whether the peptide fragment Abeta(25-35) can affect the somatostatinergic system in the rat hippocampus. Hence, Abeta(25-35) was injected intracerebroventricularly (i.c.v.) to Wistar rats in a single dose or infused via an osmotic minipump connected to a cannula implanted in the right lateral ventricle during 14 days. The animals were decapitated 7 or 14 days after the single injection and 14 days after chronic infusion of the peptide. Chronic i.c.v. infusion of Abeta(25-35) decreased SRIF-like immunoreactive content without modifying the SRIF receptor density, SRIF receptor expression, or the Gialpha(1), Gialpha(2), and Gialpha(3) protein levels in the hippocampus. This treatment, however, caused a decrease in basal and forskolin-stimulated AC activity as well as in the capacity of SRIF to inhibit AC activity. Furthermore, the protein levels of the neural-specific AC type I were significantly decreased in the hippocampus of the treated rats, whereas an increase in the levels of AC V/VI was found, with no alterations in type VIII AC. A single i.c.v. dose of Abeta(25-35) exerted no effect on SRIF content or SRIF receptors but induced a slight decrease in forskolin-stimulated AC activity and its inhibition by SRIF. Because chronic Abeta(25-35) infusion impairs learning and memory whereas SRIF facilitates these functions, the alterations described here might be physiologically important given the decreased cognitive behavior previously reported in Abeta-treated rats.

Adenylyl Cyclases↗
PubMed2007

Beta-adrenoceptor blocker treatment and the cardiac beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in chronic heart failure.

Recent studies showed that chronic beta-adrenoceptor (AR) blocker treatment exerts beneficial effects in patients with chronic heart failure (CHF). In CHF, sympathetic drive to the heart is increased, and this causes pathological changes in cardiac beta-AR-G-protein(s)-adenylyl cyclase system: Cardiac beta-1 AR are decreased, and amount and activity of cardiac G(i)-protein and G-protein-coupled receptor kinase (GRK) are increased resulting in diminished cardiac beta-AR functional responsiveness. One possible mechanism of beneficial effects of beta-AR blockers could be that they prevent adverse effects of increased sympathetic activity and up-regulate cardiac (and vascular) beta-AR density, and by this, enhance beta-AR-mediated effects. Another possibility could be that chronic beta-AR blocker treatment normalizes activity of G(i)-protein and may thereby restore beta-AR functional responsiveness. Moreover, failing human heart exhibits an inverse force-frequency relationship. beta-AR blockers reduce heart rate; this may, therefore, improve force of contraction. One of the strongest stimuli to activate GRK is increased sympathetic activity (as in CHF) via beta-AR stimulation. beta-AR blockers, by blocking beta-AR, can prevent GRK activation and/or can reduce the (previously enhanced) GRK activity, and this might-at least partly-contribute to beneficial effects of beta-AR blockers in CHF treatment. Finally, the "loss-of-function" Arg389Gly beta-1 AR polymorphism seems to determine heart rate and blood pressure responses to beta-1 AR blocker administration: Arg389Arg beta-1 AR subjects exhibit stronger effects than subjects with one or two Gly389 alleles. Thus, it might be predicted that patients homozygous Arg389 beta-1 AR should be good responders, whereas patients homozygous Gly389 beta-1 AR polymorphism should be poor or non-responders.

Adenylyl Cyclases↗