Cyclic AMP efflux is regulated by occupancy of the adenosine receptor in pig aortic smooth muscle cells.

Fehr, T F; Dickinson, Ellen S.; Goldman, S J; Slakey, Linda L.

doi:10.1016/s0021-9258(19)38544-8

Cited by 37 publications

(2 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, two studies with transformed cells reported a reduction with about 60 and 80% in the presence of theophylline (1 mM) and IBMX (1 mM), respectively (Ørbo et al, 1995;Millul et al, 1996). Methylxanthines appear to depress cAMP efflux through adenosine receptors (Fehr et al, 1990). If the same mechanism applies to their effect on the cellular cGMP export, an overexpression of these receptors in transformed cells may account for the more pronounced inhibition.…”

Section: Discussionmentioning

confidence: 93%

Cyclic AMP Stimulates the Cyclic GMP Egression Pump in Human Erythrocytes: Effects of Probenecid, Verapamil, Progesterone, Theophylline, IBMX, Forskolin, and Cyclic AMP on Cyclic GMP Uptake and Association to Inside-Out Vesicles

et al. 1998

View full text Add to dashboard Cite

The knowledge about the structure and function of the protein families responsible for cGMP synthesis and metabolic conversion has grown vastly the last years, whereas little is known about proteins that account for the cellular export of cGMP. In the present study, we have employed a model with inside-out vesicles prepared from human erythrocytes to characterize modulation and regulation of cellular cGMP extrusion. The active transport was saturable (Km of 2.4 +/- 0.2 microM, mean +/- SEM, n = 3) and coupled to ATP hydrolysis since no accumulation was detected in the presence of ATP-gamma-S and AMP-PNP. The observation that 100 microM of cAMP caused a minimal inhibition (14.4 +/- 0.3%) of active cGMP transport showed that the extrusion system for cGMP was not shared with cAMP, but a competitive interaction occurred for the ATP-independent association to the inside out vesicles. In contrast, the lowest, but physiological relevant cAMP concentrations (0.1-5 microM) stimulated the active cGMP transport with 30-35%, an observation that suggests cAMP as an allosteric regulator of the cGMP transporter. Several well-known modulators of other energy-requiring membrane transport systems caused a competitive and concentration-dependent inhibition, including verapamil (Ki = 13.0 +/- 2.4 microM), forskolin (Ki = 13.5 +/- 1.4 microM) and probenecid (Ki = 27.0 +/- 1.3 microM). Progesterone, which was the most potent inhibitor (Ki = 2.2 +/- 0.3 microM), interacted with the active cGMP transport in a noncompetitive manner. The highest concentration (100 microM) of IBMX and theophylline reduced the active cGMP uptake with 29.5 +/- 1.9% and 21.6 +/- 2.1%, respectively. None of these substances interfered with the association of cGMP to the vesicles in absence of ATP. The present results show that human erythrocytes possess a cell membrane cGMP transporter which is coupled to an ATPase. Its activity is regulated by cAMP in an apparent allosteric manner and inhibited by substances previously known to interact with other membrane transport systems.

show abstract

Section: Discussionmentioning

confidence: 93%

Cyclic AMP Stimulates the Cyclic GMP Egression Pump in Human Erythrocytes: Effects of Probenecid, Verapamil, Progesterone, Theophylline, IBMX, Forskolin, and Cyclic AMP on Cyclic GMP Uptake and Association to Inside-Out Vesicles

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Action. In many cells, ligand-induced activation of adenylate cyclase leads to both accumulation of intracellular cAMP and increased efflux of cAMP [reviewed in Brunton and Heasley (1988); Fehr et al, 1990). As shown in Figure 1, a significant proportion of the cAMP synthesized by Bi6Fio cells in response to a-MSH is secreted into the extracellular medium.…”

Section: Time Dependence Of Camp Accumulation and Agoutimentioning

confidence: 99%

Agouti Antagonism of Melanocortin Binding and Action in the B16F10 Murine Melanoma Cell Line

Blanchard

Harris²,

Ittoop³

et al. 1995

Biochemistry

View full text Add to dashboard Cite

Several dominant mutations at the murine agouti locus result in the expression of a number of phenotypic changes, including a predominantly yellow coat color, obesity, and hyperinsulinemia. The mutants exhibit ectopic overexpression of normal agouti protein, suggesting that agouti regulates coat coloration by direct antagonism of the alpha-melanocyte-stimulating hormone receptor. We have tested this hypothesis by examining agouti inhibition of both melanocortin-stimulated cyclic adenosine monophosphate production and the binding of a radioactive melanocortin analog in the murine B16F10 melanoma cell line. Inhibition of melanocortin-induced cyclic nucleotide accumulation did not require preincubation of the cells with agouti and was independent of the agonist used. Furthermore, inhibition of both agonist binding to and activation of melanocortin receptor could be described by a simple competitive model with similar inhibition constants of 1.9 and 0.9 nM, respectively. The mutually exclusive binding of agouti and melanocortin was verified by cross-linking experiments using a radiolabeled alpha-melanocyte-stimulating hormone analog. Competitive inhibition of alpha-melanocyte-stimulating hormone binding can account for the effects of agouti on coat coloration and suggests the possibility that the other phenotypic changes observed on agouti overexpression may be due to direct action of agouti at a novel melanocortin receptor(s).

show abstract

cAMP‐dependent protein kinase: structure, function and control

Bossemeyer¹,

Kinzel²,

Reed³

1996

Protein Phosphorylation

View full text Add to dashboard Cite

Cyclic AMP efflux is regulated by occupancy of the adenosine receptor in pig aortic smooth muscle cells.

Cited by 37 publications

References 25 publications

Cyclic AMP Stimulates the Cyclic GMP Egression Pump in Human Erythrocytes: Effects of Probenecid, Verapamil, Progesterone, Theophylline, IBMX, Forskolin, and Cyclic AMP on Cyclic GMP Uptake and Association to Inside-Out Vesicles

Cyclic AMP Stimulates the Cyclic GMP Egression Pump in Human Erythrocytes: Effects of Probenecid, Verapamil, Progesterone, Theophylline, IBMX, Forskolin, and Cyclic AMP on Cyclic GMP Uptake and Association to Inside-Out Vesicles

Agouti Antagonism of Melanocortin Binding and Action in the B16F10 Murine Melanoma Cell Line

cAMP‐dependent protein kinase: structure, function and control

Contact Info

Product

Resources

About