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Calcium- and cyclic-AMP-mediated secretory responses in isolated colonic crypts

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Abstract

Whole-cell recordings were performed at isolated crypts from the distal colon of the rat. Enterocytes in intact crypts, patched from the basolateral side, exhibited a gradient in the resting zero-current potential. Along the axis of the crypt, the highest potentials were measured in the ground region, the lowest in the surface region. The cholinergic agonist, carbachol, induced a hyperpolarization and an increase of the outward current in both the middle and the ground cells of intact crypts. This effect could be prevented by Ba2+ or by the intracellular Ca2+ antagonist, 8-(N, N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8). Its action, however, was not dependent on the presence of external Ca2+. Both ground cells and the cells in the middle part of the crypt responded to forskolin, an activator of the adenylate cyclase, with a depolarization. In the middle part of the crypt, the depolarization induced by forskolin was associated with an increase of the outward current. It could be blocked by the Cl− channel blocker, 5-nitro-2-(3-phenylpropylamino)-benzoate, indicating an increase of Cl− conductance. In contrast, the forskolin-induced depolarization in the ground part of the crypt was associated with a decrease of the outward current. This effect could be prevented by Ba2+, indicating a decrease of a potassium conductance. The changes in outward current could be prevented by the presence of an inhibitor of protein kinase A in the pipette solution. In conclusion, these results suggest that carbachol, an agonist acting on the Ca2+ pathway, indirectly causes Cl− secretion by an increase of the driving force, i.e. the membrane potential. Only the activation of cyclic AMP synthesis by forskolin is able to increase Cl− conductance in the rat colon. The latter response seems to be dependent on the state of differentiation of the enterocytes.

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, W-6650, Homburg/Saar, Federal Republic of Germany

    M. Böhme, M. Diener & W. Rummel

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  1. M. Böhme
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  2. M. Diener
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  3. W. Rummel
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Böhme, M., Diener, M. & Rummel, W. Calcium- and cyclic-AMP-mediated secretory responses in isolated colonic crypts. Pflügers Arch. 419, 144–151 (1991). https://doi.org/10.1007/BF00373000

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