Unique Inactivation Properties of NAADP-sensitive CaGraphic Release (*)

  1. Armando A. Genazzani(§),
  2. Ruth M. Empson and
  3. Antony Galione
  1. From the Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom
  1. § To whom correspondence should be addressed. Tel.: 44-1865-271890; Fax: 44-1865-271853; armando.genazzani{at}pharm.ox.ac.uk.

Abstract

CaGraphic mobilization from intracellular stores constitutes an important mechanism for generating cytoplasmic CaGraphic signals. Inositol trisphosphate (InsPGraphic) and ryanodine receptors are the two families of intracellular CaGraphic release channels that have been identified, which may be regulated by separate intracellular messengers, InsPGraphic and cyclic adenosine 5′-diphosphate ribose, respectively. A third molecule, nicotinic acid adenine dinucleotide phosphate (NAADP), has recently been recognized as a potent CaGraphic releasing agent in sea urchin eggs and microsomes. We now report that non-releasing concentrations of NAADP fully and irreversibly inactivate the NAADP-sensitive CaGraphic release mechanism. This phenomenon occurred both in intact sea urchin eggs and in homogenates and is not shared by either InsPGraphic or cyclic adenosine 5′-diphosphate ribose. The novel properties of this CaGraphic release mechanism, giving a one-shot CaGraphic release, may be suited to irreversible cellular events.

Footnotes

  • * The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • 1 The abbreviations used are:

    InsPGraphic

    inositol trisphosphate

    cADPR

    cyclic adenosine 5′-diphosphate ribose

    NAADP

    nicotinic acid adenine dinucleotide phosphate

    Pipes

    1,4-piperazinediethanesulfonic acid.

    • Received March 7, 1996.
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