beta-Adrenergic activation of electrogenic K+ and Cl- secretion in guinea pig distal colonic epithelium proceeds via separate cAMP signaling pathways.

نویسندگان

  • Susan T Halm
  • Jin Zhang
  • Dan R Halm
چکیده

Adrenergic stimulation of isolated guinea pig distal colonic mucosa produced transient Cl(-) and sustained K(+) secretion. Transient short-circuit current (I(sc)) depended on beta(2)-adrenergic receptors (beta(2)-AdrR), and sustained I(sc) relies on a beta(1)-AdrR/beta(2)-AdrR complex. Epinephrine (epi) increased cAMP content with a biphasic time course similar to changes in epi-activated I(sc) ((epi)I(sc)). Inhibition of transmembrane adenylyl cyclases (tmACs) reduced peak (epi)I(sc) and cAMP to near zero without decreasing sustained (epi)I(sc), consistent with cAMP from tmAC signaling for only Cl(-) secretion. Inhibition of soluble adenylyl cyclase (sAC) reduced sustained (epi)I(sc) and cAMP to near zero without decreasing peak (epi)I(sc) or cAMP, consistent with cAMP from sAC signaling for K(+) secretion. Sensitivity to phosphodiesterase (PDE) inhibitors and peptide YY (PYY) stimulation further supported separate signaling for the two components. PDE3 or PDE4 inhibitors enhanced peak (epi)I(sc) but not sustained (epi)I(sc), consistent with these PDEs as part of the beta(2)-AdrR signaling domain. PYY suppressed peak (epi)I(sc) in a pertussis toxin (PTx)-sensitive manner, supporting Galpha(i)-dependent inhibition of tmACs producing cAMP for Cl(-) secretion. Since PYY or PTx did not alter sustained (epi)I(sc), signaling for K(+) secretion occurred via a Galpha(i)-independent mechanism. Presence of multiple sAC variants in colonic epithelial cells was supported by domain-specific antibodies. Responses to specific activators and inhibitors suggested that protein kinase A was not involved in activating peak or sustained components of (epi)I(sc), but the cAMP-dependent guanine nucleotide exchange factor, Epac, may contribute. Thus beta-adrenergic activation of electrogenic Cl(-) and K(+) secretion, respectively, required tmAC- and sAC-dependent signaling pathways.

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-Adrenergic activation of electrogenic K and Cl secretion in guinea pig distal colonic epithelium proceeds via separate cAMP signaling pathways

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عنوان ژورنال:
  • American journal of physiology. Gastrointestinal and liver physiology

دوره 299 1  شماره 

صفحات  -

تاریخ انتشار 2010