| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
TRANSLATIONAL PHYSIOLOGY
2C-adrenoceptor expression: role in serum induction in human arteriolar smooth muscle cells
Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio
Submitted 30 December 2003 ; accepted in final form 19 August 2004
The physiological role of 
2-adrenoceptors (2-ARs) in cutaneous, arteriolar, vascular smooth muscle cells (VSMs) is to mediate cold-induced constriction. In VSMs cultured from human cutaneous arterioles, there is a selective increase in 2C-AR expression after serum stimulation. In the present study, we examined the cellular mechanisms contributing to this response. Serum induction of 2C-ARs was paralleled by increased expression of cyclooxygenase-2 (COX-2), increased release of prostaglandins, and increased intracellular concentration of cAMP. Inhibition of COX-2 by acetyl salicylic acid (1 mM), NS-398 (5 µM), or celecoxib (3 µM) abolished the increase in cAMP and markedly reduced 2C-AR induction in response to serum stimulation. The cAMP agonists, forskolin (10 µM), isoproterenol (10 µM), and cholera toxin (0.1 µg/ml) each dramatically increased expression of 2C-ARs in human cutaneous VSMs. The A-kinase inhibitor H-89 (2 µM) inhibited phosphorylation of cAMP response element binding protein, but not the increase in 2C-AR expression in response to these agonists. cAMP-dependent but A-kinase independent signaling can involve activation of guanine nucleotide exchange factors for the GTP-binding protein, Rap. Indeed, pull-down assays demonstrated Rap1 activation by serum and forskolin in VSM. Transient transfections using 2C-AR promoter-luciferase reporter construct demonstrated that Rap1 increased reporter activity, whereas the A-kinase catalytic subunit decreased reporter activity. These results indicate that cAMP signaling can have dual effects in cutaneous VSMs:activation of 2C-AR transcription mediated by Rap1 GTPase and suppression mediated by A-kinase. The former effect predominates in serum-stimulated VSMs leading to a COX-2, cAMP, and Rap 1-dependent increase in 2C-AR expression. Such increased expression of 2C-ARs may contribute to enhanced cold-induced vasoconstriction and Raynaud's phenomenon.
microcirculation; cyclooxygenase-2; Rap GTPase; A kinase
This article has been cited by other articles:
|
|
 |
|
  A. H. Eid, M. A. Chotani, S. Mitra, T. J. Miller, and N. A. Flavahan Cyclic AMP acts through Rap1 and JNK signaling to increase expression of cutaneous smooth muscle {alpha}2C-adrenoceptors Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H266 - H272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Eid, K. Maiti, S. Mitra, M. A. Chotani, S. Flavahan, S. R. Bailey, C. S. Thompson-Torgerson, and N. A. Flavahan Estrogen increases smooth muscle expression of {alpha}2C-adrenoceptors and cold-induced constriction of cutaneous arteries Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1955 - H1961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhou, S. Mitra, S. Varadharaj, N. Parinandi, J. L. Zweier, and N. A. Flavahan Increased Expression of Cyclooxygenase-2 Mediates Enhanced Contraction to Endothelin ETA Receptor Stimulation in Endothelial Nitric Oxide Synthase Knockout Mice Circ. Res., June 9, 2006; 98(11): 1439 - 1445. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Krajnak, R. G. Dong, S. Flavahan, D. Welcome, and N. A. Flavahan Acute vibration increases {alpha}2C-adrenergic smooth muscle constriction and alters thermosensitivity of cutaneous arteries J Appl Physiol, April 1, 2006; 100(4): 1230 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Bailey, S. Mitra, S. Flavahan, and N. A. Flavahan Reactive oxygen species from smooth muscle mitochondria initiate cold-induced constriction of cutaneous arteries Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H243 - H250. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
