![]() |
|
|
BN Atkinson and KP Minneman
Department of Pharmacology, Emory University Medical School, Atlanta, Georgia 30322.
The effect of norepinephrine (NE) on cAMP accumulation in primary glial cultures is mediated by two functionally opposing receptor subtypes. beta-Adrenergic receptor activation increases cAMP formation, whereas simultaneous alpha 2-adrenergic receptor activation partially inhibits this effect. We compared desensitization of these two responses during exposure to selective agonists or NE. Pretreatment with the beta- selective agonist isoproterenol (ISO) decreased responses to ISO, ISO plus the alpha 2-selective agonist UK 14,304 (UK), and NE. However, ISO plus UK and NE responses decreased more, relative to their control values, than did responses to ISO alone. Pretreatment with UK increased cAMP responses to both ISO and forskolin (sensitization), with little effect on alpha 2-mediated inhibition of these responses. Pretreatment with NE caused effects similar to those of both ISO and UK pretreatment. NE pretreatment decreased responses to ISO, ISO plus UK, and NE, sensitized responses to forskolin, and had little effect on alpha 2-mediated inhibition. Thus, chronic agonist exposure desensitizes beta-adrenergic receptors more rapidly and at much lower concentrations than alpha 2-adrenergic receptors in these cultures. The continuing alpha 2 inhibition during diminishing beta stimulation functionally accelerates the loss of the NE response.
This article has been cited by other articles:
![]() |
S. Cikos, P. Rehak, S. Czikkova, J. Vesela, and J. Koppel Expression of adrenergic receptors in mouse preimplantation embryos and ovulated oocytes Reproduction, June 1, 2007; 133(6): 1139 - 1147. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. C. Prinster, T. G. Holmqvist, and R. A. Hall {alpha}2C-Adrenergic Receptors Exhibit Enhanced Surface Expression and Signaling upon Association with beta2-Adrenergic Receptors J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 974 - 981. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. N. Desai, K. M. Standifer, and D. C. Eikenburg Cellular G Protein-Coupled Receptor Kinase Levels Regulate Sensitivity of the {alpha}2B-Adrenergic Receptor to Undergo Agonist-Induced Down-Regulation J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 767 - 773. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. N. Desai, K. M. Standifer, and D. C. Eikenburg Simultaneous {alpha}2B- and {beta}2-Adrenoceptor Activation Sensitizes the {alpha}2B-Adrenoceptor for Agonist-Induced Down-Regulation J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 794 - 802. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Xu, J. He, A. M. Castleberry, S. Balasubramanian, A. G. Lau, and R. A. Hall Heterodimerization of alpha 2A- and beta 1-Adrenergic Receptors J. Biol. Chem., March 14, 2003; 278(12): 10770 - 10777. [Abstract] [Full Text] [PDF] |
||||