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

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 297; no. 2; pp. G269 - G277
• Main Authors: Zhang, Jin, Halm, Susan T., Halm, Dan R.
• Format: Journal Article
• Language: English
• Published: American Physiological Society 01.08.2009
• Subjects: Hormones and Signaling
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00076.2009

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 α-AdrR antagonists BE2254 (α1-AdrR) and yohimbine (α2-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 EC 50 s 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.