A multifunctional, ubiquitous molecule, adenosine acts at cell-surface G protein-coupled receptors, as well numerous enzymes, including protein kinases and adenylyl cyclase. Extracellular is thought to be produced either by export or metabolism, predominantly through ecto-5’-nucleotidase activity (also producing inorganic phosphate). It inactivated extracellular metabolism via deaminase ammonia...

The cAMP-signaling pathway is composed of multiple components ranging from receptors, G proteins, and adenylyl cyclase to protein kinase A. A common view of the molecular interaction between them is that these molecules are disseminated on the plasma lipid membrane and random collide with each other to transmit signals. A limitation to this idea, however, is that a signaling cascade involving m...

A functional impairment in vasodilator tone may be important in the pathogenesis and/or maintenance of elevated peripheral vascular resistance in hypertension. Previous studies of hypertensive subjects have demonstrated impaired beta-adrenergic-mediated vasodilation paralleling a reduction in lymphocyte beta-adrenergic-stimulated adenylyl cyclase activity. We have suggested that this impairment...

Short-term activation of G i/o-coupled receptors inhibits adenylyl cyclase, whereas persistent activation of G i/o-coupled receptors results in a compensatory sensitization of adenylyl cyclase activity after subsequent activation by G s or forskolin. Several indirect observations have suggested the involvement of increased G s-adenylyl cyclase interactions in the expression of sensitization; ho...

Objective—cAMP is a critical regulator of metabolic and cardiovascular function. However, the role of genetic variability in the regulation of cAMP-mediated effects is unclear. Therefore, we assessed the effect of the expression of a recently identified missense genetic variant of adenylyl cyclase isoform 6 (ADCY6 S674). Methods and Results—In rat vascular smooth muscle cells, gene transfer of ...

We report here that, contrary to previously reported findings, treatment of S49 wild-type (WT) lymphoma cells with 0-50 nM epinephrine resulted in a heterologous desensitization of adenylyl cyclase (EC 4.6.1.1)--that is, epinephrine and prostaglandin E1 (PGE1) stimulations of adenylyl cyclase were reduced. Observation of this heterologous desensitization required the assay of adenylyl cyclase w...

Intracellular calcium and cAMP are the 2 second messengers that regulate renin release; cAMP stimulates renin release from juxtaglomerular (JG) cells, whereas increased intracellular calcium inhibits it. We hypothesized that decreased intracellular calcium acts by activating calcium-inhibitable isoforms of adenylyl cyclase, increasing cAMP, and stimulating renin secretion. We used a primary cul...

To assess the effects of oxyradicals on cardiac beta-adrenoceptors, G-proteins and adenylyl cyclase, rat heart membranes were incubated with xanthine (X) plus xanthine oxidase (XO) for different intervals. The basal as well as forskolin-, NaF-, 5'-guanylylimidodiphosphate and isoproterenol-stimulated adenylyl cyclase activities showed an increase at 10 min and a decrease at 30 min of incubation...

The prototypical second messenger cAMP regulates a wide variety of physiological processes. It can simultaneously mediate diverse functions by acting locally in independently regulated microdomains. In mammalian cells, two types of adenylyl cyclase generate cAMP: G-protein-regulated transmembrane adenylyl cyclases and bicarbonate-, calcium- and ATP-regulated soluble adenylyl cyclase (sAC). Beca...

It is demonstrated here that in Escherichia coli, the phosphorylated form of the glucose-specific phosphocarrier protein IIA(Glc) of the phosphoenolpyruvate:sugar phosphotransferase system is an activator of adenylyl cyclase and that unphosphorylated IIA(Glc) has no effect on the basal activity of adenylyl cyclase. To elucidate the specific role of IIA(Glc) phosphorylation in the regulation of ...