Affiliation:
1. Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio
Abstract
Adrenergic stimulation of isolated guinea pig distal colonic mucosa produced transient Cl− and sustained K+ secretion. Transient short-circuit current ( Isc) depended on β2-adrenergic receptors (β2-AdrR), and sustained Isc relies on a β1-AdrR/β2-AdrR complex. Epinephrine (epi) increased cAMP content with a biphasic time course similar to changes in epi-activated Isc (epi Isc). Inhibition of transmembrane adenylyl cyclases (tmACs) reduced peak epi Isc and cAMP to near zero without decreasing sustained epi Isc, consistent with cAMP from tmAC signaling for only Cl− secretion. Inhibition of soluble adenylyl cyclase (sAC) reduced sustained epi Isc and cAMP to near zero without decreasing peak epi Isc 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 Isc but not sustained epi Isc, consistent with these PDEs as part of the β2-AdrR signaling domain. PYY suppressed peak epi Isc in a pertussis toxin (PTx)-sensitive manner, supporting Gαi-dependent inhibition of tmACs producing cAMP for Cl− secretion. Since PYY or PTx did not alter sustained epi Isc, signaling for K+ secretion occurred via a Gαi-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 Isc, but the cAMP-dependent guanine nucleotide exchange factor, Epac, may contribute. Thus β-adrenergic activation of electrogenic Cl− and K+ secretion, respectively, required tmAC- and sAC-dependent signaling pathways.
Publisher
American Physiological Society
Subject
Physiology (medical),Gastroenterology,Hepatology,Physiology
Cited by
33 articles.
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