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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/G269    most recent 00076.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Google Scholar Articles by Zhang, J. Articles by Halm, D. R. PubMed PubMed Citation Articles by Zhang, J. Articles by Halm, D. R.

HORMONES AND SIGNALING

Adrenergic activation of electrogenic K⁺ secretion in guinea pig distal colonic epithelium: involvement of β1- and β2-adrenergic receptors

Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio

Submitted 2 March 2009 ; accepted in final form 16 May 2009

Adrenergic stimulation of electrogenic K⁺ secretion in isolated mucosa from guinea pig distal colon required activation of two β-adrenergic receptor subtypes (β-AdrR). Addition of epinephrine (epi) or norepinephrine (norepi) to the bathing solution of mucosae in Ussing chambers increased short-circuit current (I_sc) and transepithelial conductance (G_t), consistent with this cation secretion. A β-adrenergic classification was supported by propranolol antagonism of this secretory response and the lack of effect by the -AdrR antagonists BE2254 (1-AdrR) and yohimbine (2-AdrR). Subtype-selective antagonists CGP20712A (β1-AdrR), ICI-118551 (β2-AdrR), and SR59320A (β3-AdrR) were relatively ineffective at inhibiting the epi-stimulated I_sc response. In combination, CGP20712A and ICI-118551 inhibited the response, which supported a synergistic action by β1-AdrR and β2-AdrR. Expression of mRNA for both β1-AdrR and β2-AdrR was indicated by RT-PCR of RNA from colonic epithelial cells. Protein expression was indicated by immunoblot showing bands at molecular weights consistent with monomers and oligomers. Immunoreactivity (ir) for β1-AdrR and β2-AdrR was prominent in basolateral membranes of columnar epithelial cells in the crypts of Lieberkühn as well as intercrypt surface epithelium. Cells in the pericryptal sheath also had β1-AdrR^ir but did not have discernable β2-AdrR^ir. The adrenergic sensitivity of K⁺ secretion measured by I_sc and G_t was relatively low as indicated by EC₅₀s of 41 ± 7 nM for epi and 50 ± 14 nM for norepi. Adrenergic activation of electrogenic K⁺ secretion required the involvement of both β1-AdrR and β2-AdrR, occurring with an agonist sensitivity reduced compared with reported values for either receptor subtype.

epinephrine; norepinephrine; isoproteranol; CGP20712A; ICI-118551

This article has been cited by other articles:

				J. Zhang, S. T. Halm, and D. R. Halm Adrenergic activation of electrogenic K+ secretion in guinea pig distal colonic epithelium: desensitization via the Y2-neuropeptide receptor Am J Physiol Gastrointest Liver Physiol, August 1, 2009; 297(2): G278 - G291. [Abstract] [Full Text] [PDF]