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Am J Physiol Gastrointest Liver Physiol 294: G738-G747, 2008. First published January 10, 2008; doi:10.1152/ajpgi.00239.2007
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HORMONES AND SIGNALING

Suppression of carbachol-induced oscillatory Cl secretion by forskolin in rat parotid and submandibular acinar cells

Takahide Shintani, Chikara Hirono, Makoto Sugita, Yoshiko Iwasa, and Yoshiki Shiba

Department of Oral Physiology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan

Submitted 27 May 2007 ; accepted in final form 8 January 2008

Sympathetic stimulation induces weak salivation compared with parasympathetic stimulation. To clarify this phenomenon in salivary glands, we investigated cAMP-induced modulation of Ca2+-activated Cl secretion from rat parotid and submandibular acinar cells because fluid secretion from salivary glands depends on the Cl secretion. Carbachol (Cch), a Ca2+-increasing agent, induced hyperpolarization of the cells with oscillatory depolarization in the current clamp mode of the gramicidin-perforated patch recording. In the voltage clamp mode at –80 mV, Cch induced a bumetanide-sensitive oscillatory inward current, which was larger in rat submandibular acinar cells than in parotid acinar cells. Forskolin and IBMX, cAMP-increasing agents, did not induce any marked current, but they evoked a small nonoscillatory inward current in the presence of Cch and suppressed the Cch-induced oscillatory inward current in all parotid acinar cells and half (56%) of submandibular acinar cells. In the current clamp mode, forskolin + IBMX evoked a small nonoscillatory depolarization in the presence of Cch and reduced the amplitude of Cch-induced oscillatory depolarization in both acinar cells. The oscillatory inward current estimated at the depolarized membrane potential was suppressed by forskolin + IBMX. These results indicate that cAMP suppresses Ca2+-activated oscillatory Cl secretion of parotid and submandibular acinar cells at –80 mV and possibly at the membrane potential during Cch stimulation. The suppression may result in the weak salivation induced by sympathetic stimulation.

Na+-K+-2Cl cotransporter; Cl channel; cAMP; gramicidin-perforated patch recording; bumetanide



Address for reprint requests and other correspondence: C. Hirono, Dept. of Oral Physiology, Hiroshima Univ. Graduate School of Biomedical Sciences, 2-3 Kasumi 1-Chome, Minami-ku, Hiroshima 734-8553, Japan (e-mail: chikara{at}hiroshima-u.ac.jp)







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