Differing effects of apical and basolateral adenosine on colonic epithelial cell line T84

Abstract

Adenosine and its agonists, 5'-(N-ethylcarboxamido)adenosine and N6-(D-2-phenylisopropyl)-adenosine, induced a sustained increase in chloride secretion when added to either the apical or basolateral aspect of monolayers of the human colonic epithelial cell line T84. Secretion was induced with identical kinetics by addition to both sides, but apical addition was less potent. The rank order of potency of the agonists on either side was consistent with the presence of an adenosine A2-receptor, but the apical and basolateral receptors differed in both their ability to stimulate increases in adenosine 3',5'-cyclic monophosphate, and their susceptibility to down-modulation by chronic exposure to 5'-(N-ethylcarboxamido) adenosine in culture.

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

“…7, C and D). The sustained component of this negative I sc response was via adenosine action, which differs from the Cl Ϫ secretory response of T84 cells to mucosal adenosine (3). Similar to mouse and rat colon (28,35), the transient component in guinea pig distal colon apparently was activated by unmodified ATP (Fig.…”

PepT1-mediated epithelial transport of dipeptides and cephalexin is enhanced by luminal leptin in the small intestine

“…In a number of polarized epithelial cell lines, several receptors belonging to the cytokine receptor family have been shown to produce different biological responses according to their apical or basolateral localization. This is the case for EGF receptors (53), adenosine receptors (54,55), and chemokine receptors (56). In enterocytes, the apical receptor for HGF, c-Met, activates growth and differentiation through an src-related kinase, gastrointestinal tyrosine kinase (57).…”

Surface expression, polarization, and functional significance of CD73 in human intestinal epithelia.

“…As another potential means of physiological regulation of CD73, we used conditions known to induce down-regulation of the T84 response to adenosine to determine if the converting ecto-enzyme and adenosine receptor surface expression were regulated in synchronous or asynchronous fashion. Overnight exposure of monolayers to the nonmetabolizable adenosine analogue N-ethylcarboxamidoadenosine (NECA [28]) down-regulated adenosine receptor signal transduction while not influencing other agonist mediated Cl Ϫ secretory pathways that signal through the same second messenger/kinase cascade (Isc responses to 10 M of adenosine applied apically were 3.1Ϯ1.2 A/cm 2 vs. 41Ϯ6 A/cm 2 for NECA preexposed and control monolayers, respectively; the Cl Ϫ secretory responses to 100 M of the cAMP-mediated agonist forskolin for the same conditions were 63Ϯ12 A/cm 2 vs. 63Ϯ5 A/cm 2 , respectively; meanϮSE, n ϭ 4). These data confirm that long-term NECA exposure selectively down-regulates elements of the adenosine-stimulated secretory pathway but that CD73, the ectoenzyme in this pathway, is independently regulated from the receptor.…”