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Responsive properties of principal cells in the pineal gland (pinealocytes) of rodents (ddy mice and Wistar rats) were studied using a whole-cell patch-electrode. The pineal gland is one of the circumventricular organs in the brain and thus possesses an incomplete blood-brain barrier. When external saline containing 10 microM nicotine was applied from a "Y tube" to pinealocytes, which were whole-cell clamped at -50 mV, definite inward currents were induced. Other nicotinic agonists, including ACh (10 microM), choline (1 mM), lobeline (10 microM) and cytisine (10 microM), also induced inward currents. However, time courses and amplitude as well as recovery from desensitization of the agonist-evoked currents showed variation among cells, indicating heterogeneity of functional nicotinic ACh receptors expressed in these cells. For nicotine-induced currents in the pinealocytes of ddy mice, the I-V relationship measured with a saw-tooth voltage clamp showed reversal potential near -5 mV. Notably, in previous morphological studies on mammalian pineal glands, the presence of cholinergic fibers innervating pinealocytes was found. To determine whether nicotinic synaptic transmission in pinealocytes occurs in vivo, external saline containing 20 mM KCl was applied from a "Y tube" to pinealocytes, but no typical excitatory postsynaptic currents were detected from the preparations of ddy mice. (Supported by a grant from Smoking Research Foundation, Japan) [J Physiol Sci. 2007;57 Suppl:S233]