Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Stimulation of Arachidonic Acid Release and Inhibition of Mitogenesis by Cloned Genes for Muscarinic Receptor Subtypes Stably Expressed in A9 L Cells

Bruce R. Conklin, Mark R. Brann, Noel J. Buckley, Alice L. Ma, Tom I. Bonner and Julius Axelrod
Proceedings of the National Academy of Sciences of the United States of America
Vol. 85, No. 22 (Nov. 15, 1988), pp. 8698-8702
Stable URL: http://www.jstor.org/stable/32811
Page Count: 5
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Stimulation of Arachidonic Acid Release and Inhibition of Mitogenesis by Cloned Genes for Muscarinic Receptor Subtypes Stably Expressed in A9 L Cells
Preview not available

Abstract

A family of genes encoding four distinct muscarinic receptors (designated m1-m4) has been cloned and stably expressed in A9 L cells. When the m1 and m3 receptors were stimulated with carbachol, there was a rapid rise of liberated arachidonic acid, inositol phosphates, and cAMP, while m2 and m4 receptor stimulation had no detectable stimulation of these second messengers. Pretreatment with phorbol 12-myristate 13-acetate (PMA) caused a marked acceleration and amplification of m1 and m3 receptor-mediated arachidonic acid release. In contrast, m1- and m3-mediated inositol phosphate formation was inhibited by the same PMA pretreatment. Arachidonic acid release was unaffected by manipulations of cAMP levels. Arachidonic acid production was inhibited by calcium-free medium and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8; an inhibitor of cytosolic calcium mobilization) yet was unaffected by verapamil, a calcium-channel blocker. These experiments show that arachidonic acid release induced by the m1 and m3 receptors is regulated independently of phospholipase C and cAMP accumulation. Carbachol stimulation of the m1 and m3 receptors also markedly decreased mitogenesis as measured by thymidine incorporation. The m1 receptor-mediated inhibition of mitogenesis could be partially blocked by indomethacin, a cyclooxygenase inhibitor. The inhibition of mitogenesis could be mimicked by cAMP elevation.

Page Thumbnails

  • Thumbnail: Page 
8698
    8698
  • Thumbnail: Page 
8699
    8699
  • Thumbnail: Page 
8700
    8700
  • Thumbnail: Page 
8701
    8701
  • Thumbnail: Page 
8702
    8702