title: Adrenergic activation of electrogenic K+ secretion in guinea pig distal colonic epithelium: involvement of beta1- and beta2-adrenergic receptors.
abstract: Adrenergic stimulation of electrogenic K+ secretion in isolated mucosa from guinea pig distal colon required activation of two beta-adrenergic receptor subtypes (beta-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 beta-adrenergic classification was supported by propranolol antagonism of this secretory response and the lack of effect by the alpha-AdrR antagonists BE2254 (alpha1-AdrR) and yohimbine (alpha2-AdrR). Subtype-selective antagonists CGP20712A (beta1-AdrR), ICI-118551 (beta2-AdrR), and SR59320A (beta3-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 beta1-AdrR and beta2-AdrR. Expression of mRNA for both beta1-AdrR and beta2-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 beta1-AdrR and beta2-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 beta1-AdrR(ir) but did not have discernable beta2-AdrR(ir). The adrenergic sensitivity of K+ secretion measured by Isc and Gt 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 beta1-AdrR and beta2-AdrR, occurring with an agonist sensitivity reduced compared with reported values for either receptor subtype.
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio 45435, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Susan T
authors.initials: ST
authors.lastname: Halm
authors.forename: Dan R
authors.initials: DR
authors.lastname: Halm
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007419:Intestinal Secretions; D008297:Male; D008564:Membrane Potentials; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine