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HORMONES AND SIGNALING

Adrenergic activation of electrogenic K⁺ secretion in guinea pig distal colonic epithelium: desensitization via the Y2-neuropeptide receptor

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

Submitted 2 March 2009 ; accepted in final form 20 May 2009

Adrenergic activation of electrogenic K⁺ secretion in isolated mucosa from guinea pig distal colon was desensitized by peptide-YY (PYY). Addition of PYY or neuropeptide-Y (NPY) to the bathing solution of mucosae in Ussing chambers suppressed the short-circuit current (I_sc) corresponding to electrogenic Cl^– secretion, whether stimulated by epinephrine (epi), prostaglandin-E₂ (PGE₂), or carbachol (CCh). Neither peptide markedly inhibited the large transient component of synergistic secretion (PGE₂ + CCh). Sustained Cl^– secretory I_sc was inhibited 65% by PYY or NPY, with IC₅₀s of 4.1 ± 0.9 nM and 9.4 ± 3.8 nM, respectively. This inhibition was eliminated by BIIE0246, an antagonist of the Y2-neuropeptide receptor (Y2-NpR), but not by Y1-NpR antagonist BVD10. Adrenergic sensitivity for activation of K⁺ secretion in the presence of Y2-NpR blockade by BIIE0246 was (EC₅₀s) 2.9 ± 1.2 nM for epi and 13.3 ± 1.0 nM for norepinephrine, approximately fourfold greater than in the presence of PYY. Expression of mRNA for both Y1-NpR and Y2-NpR was indicated by RT-PCR of RNA from colonic mucosa, and protein expression was indicated by immunoblot. Immunoreactivity (ir) for Y1-NpR and Y2-NpR was distinct in basolateral membranes of columnar epithelial cells in the crypts of Lieberkühn as well as intercrypt surface epithelium. Adrenergic nerves in proximity with crypts were detected by ir for dopamine-β-hydroxylase, and a portion of these nerves also contained NPY^ir. BIIE0246 addition increased secretagog-activated I_sc, consistent with in vitro release of either PYY or NPY. Thus PYY and NPY were able to suppress Cl^– secretory capacity and desensitize the adrenergic K⁺ secretory response, providing a direct inhibitory counterbalance against secretory activation.

epinephrine; norepinephrine; ATP; adenosine; Y1-neuropeptide receptor; enteric nerves; β1-adrenergic receptor; β2-adrenergic receptor

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: involvement of {beta}1- and {beta}2-adrenergic receptors Am J Physiol Gastrointest Liver Physiol, August 1, 2009; 297(2): G269 - G277. [Abstract] [Full Text] [PDF]