Adrenergic activation of electrogenic K secretion in guinea pig distal colonic epithelium: involvement of 1- and 2-adrenergic receptors

Zhang J, Halm ST, Halm DR. Adrenergic activation of electrogenic K secretion in guinea pig distal colonic epithelium: involvement of 1and 2-adrenergic receptors. Am J Physiol Gastrointest Liver Physiol 297: G269–G277, 2009. First published May 21, 2009; doi:10.1152/ajpgi.00076.2009.—Adrenergic stimulation of electrogenic K secretion in isolated mucosa from guinea pig distal colon required activation of two -adrenergic receptor subtypes ( -AdrR). Addition of epinephrine (epi) or norepinephrine (norepi) to the bathing solution of mucosae in Ussing chambers increased short-circuit current (Isc) and transepithelial conductance (Gt), consistent with this cation secretion. A -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 ( 1-AdrR), ICI-118551 ( 2-AdrR), and SR59320A ( 3-AdrR) were relatively ineffective at inhibiting the epi-stimulated Isc response. In combination, CGP20712A and ICI-118551 inhibited the response, which supported a synergistic action by 1-AdrR and 2-AdrR. Expression of mRNA for both 1-AdrR and 2-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 1-AdrR and 2-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 1-AdrR but did not have discernable 2-AdrR. The adrenergic sensitivity of K secretion measured by Isc and Gt 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 1-AdrR and 2-AdrR, occurring with an agonist sensitivity reduced compared with reported values for either receptor subtype.