Acute and Chronic Modulation of the Responsiveness of Receptor-Associated Adenylate Cyclases

  • J. P. Perkins
  • T. K. Harden
  • J. F. Harper
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 58 / 1)

Overview

Exposure of certain target cells to hormone agonists not only causes the activation of adenylate cyclase and the accumulation of cyclic AMP but sets in motion a complicated series of events designed to down-regulate the system if exposure to the agonist is extended in time. The development of refractoriness has been shown to result from a number of specifiable phenomena, each exhibiting unique kinetic properties. In a number of systems it has been demonstrated that upon exposure of cells to catecholamines there is a rapid uncoupling of β-adrenergic receptors from adenylate cyclase. This rapidly reversible event results in a selective loss of cellular responsiveness to catecholamines. With continued exposure of cells to catecholamine there occurs a slowly reversible loss of β-receptors from the cell. Evidence from several laboratories suggests that these phenomena are associated with changes in the membrane form of β-adrenergic receptors. In addition, it also has been shown that a nonspecific loss of responsiveness of adenylate cyclase can occur during incubation of cells with hormones that elevate cyclic AMP levels. At least in the C 6 rat glioma cell line, this phenomenon appears to occur as the result of a cyclic AMP-induced increase in the synthesis of a protein that confers on adenylate cyclase a reduced capacity to respond to all activators. The most detailed studies of agonist-induced refractoriness have been carried out with homogeneous cell populations maintained in vitro. However, there is widespread evidence for the occurrence of similar adaptive phenomena in vivo.

In addition to the adaptive phenomena that occur in hormone-stimulated adenylate cyclase systems, there is an increasing amount of evidence indicating that a number of neurohumoral agents can cause acute inhibition of adenylate cyclase. The fact that agonist-mediated inhibition is dependent on the presence of guanosine triphosphate suggests that these “inhibitory” receptors may directly interact with the same membrane components that are involved in activation of adenylate cyclase.

Keywords

Morphine Prostaglandin Propranolol PGE1 Neuroblastoma 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1982

Authors and Affiliations

  • J. P. Perkins
  • T. K. Harden
  • J. F. Harper

There are no affiliations available

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