Chronic elevation of circulating parathyroid hormone (PTH) is associated with decreased target cell responsiveness to PTH. To study the subcellular mechanism of this phenomenon we evaluated PTH receptors and adenylate cyclase activity in renal cortical membranes prepared before and after infusion of bovine parathyroid gland extract (PTE) into thyroparathyroidectomized dogs. PTE infusion resulte...

The effect of amiloride on the hormonal regulation of adenylate cyclase was studied in the rat anterior pituitary. The diuretic did not alter basal adenylate cyclase but augmented the enzyme activity in an irreversible manner in the presence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S) stimulated adenylate cyclase at lower concentrations and inhibited at higher concentrations. Amiloride t...

Persistent activation of Galpha(i/o)-coupled receptors results in an enhanced responsiveness of drug-stimulated adenylate cyclase activity through an unknown mechanism. This agonist-induced heterologous sensitization of drug-stimulated cyclic AMP accumulation has been proposed to be a mechanism by which cells adapt to prolonged Galpha(i/o) activation. Heterologous sensitization was examined in ...

Forskolin is commonly used to stimulate adenylate cyclase in the study of modulation of ion channels and other proteins by adenosine 3',5'-monophosphate (cAMP)-dependent second messenger systems. In addition to its action on adenylate cyclase, forskolin directly alters the gating of a single class of voltage-dependent potassium channels from a clonal pheochromocytoma (PC12) cell line. This alte...

The stereospecific binding site for propranolol in cardiac membranes was solubilized with 0.25% sodium deoxycholate. Affinity chromatography on norepinephrine-Sepharose yielded a fraction that bound (-)-propranolol with an association constant 360 times that of the (+)-enantiomer. A Scatchard plot indicated a single binding site with a dissociation constant for propran0101 of 11 + 4 nM and a co...

A gene from Rhizobium meliloti coding for an adenylate cyclase was sequenced, and the deduced protein sequence was compared with those of other known adenylate cyclases. No similarity could be detected with the procaryotic counterparts. However, striking similarity was found with the catalytic region of Saccharomyces cerevisiae adenylate cyclase, the cytoplasmic domains of bovine adenylate cycl...

Adenosine, acting via AI adenosine receptors, can inhibit adenylate cyclase activity in adipocytes. To assess the effects of chronic adenosine agonist exposure on the AI adenosine receptor system of adipocytes, rats were infused with (-)-phenylisopropyladenosine or vehicle for 6 days and membranes were prepared. Basal as wel1,as isoproterenol-, sodium fluoride-, and forskolin-stimulated adenyla...

We have studied the influence of myocardial infection with Trypanosoma cruzi on the beta-adrenergic adenylate cyclase complex in mouse myocardial membranes. The maximal rate of cAMP generation (Vmax) and the concentration of agonist associated with 50% of the maximal activity (apparent Kact) were determined for a series of agents. Six days after infection, the Vmax for isoproterenol significant...

A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase activity of 4-6 mu moles P1/hour mg-1 protein, measured in 120 mM NaC1 or KC1, w...

GTP-binding proteins have been implicated as transducers of a variety of biological signaling processes. These proteins share considerable structural as well as functional homology. Due to these similarities, it was thought that a monoclonal antibody that inhibits the light activation of the rod outer segment GTP-binding protein, tranducin (Gt), might exert some functional effect upon the G pro...