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Although serotonin (5-HT) release from enterochromaffin (EC) cells is considered to be regulated by multiple receptor-mediated mechanisms, little is known about the signal transduction in EC cells. We investigated the effects of adrenoceptor stimulation on 5-HT release from ileal tissue and intracellular calcium dynamics of epithelial cells in isolated ileal crypts in mice. Ileal tissues placed in organ bath were perfused with a buffered solution. Released 5-HT was measured using HPLC-ECD. Ileal crypts were isolated by collagenase digestion followed by moderate pipetting. Intracellular calcium dynamics were analyzed by digital video-imaging system using fura-2. NE, but not isoprenaline (Iso), induced 5-HT release from mouse ileal tissue. NE-induced 5-HT release was antagonized by yohimbine and rauwolscine, but not by prazosin and bunazosin. NE, but not Iso, also elicited a transient elevation of intracellular calcium in some EC cells. The effect of NE (1 microM) was slightly suppressed by prazosin and bunazosin, but was remarkably suppressed by yohimbine and rauwolscine. UK 14,304 and Clonidine at 10 microM significantly induced an increase in intracellular calcium concentration. NE-induced intracellular calcium dynamics was not significantly affected by timolol, Ro20-1724, rolipram and 8-bromo-cAMP. These results suggest that NE-induced 5-HT release from ileal EC cells is mediated predominantly via alpha 2-, but not beta-adrenoceptors, by a mechanism dependent on elevation of intracellular calcium concentration.

The electroencephalographic (EEG) effects of rolipram were investigated in rabbits with chronic electrode implants. Intravenous administration of rolipram at 10 to 100 micrograms/kg evoked an increase in the arousal EEG pattern period (low amplitude fast waves) in the cortical EEG and synchronization of the hippocampal theta waves with increased voltages. Rolipram at higher doses caused behavioral excitation in rabbits. Rolipram did not affect EEG arousal responses to both auditory stimulation (2000 Hz, monotone) and electrical stimulation (100 Hz, 0.1 msec, 3-6 V) of the midbrain reticular formation or the posterior hypothalamus. The recruiting response induced by centromedian thalamic stimulation at a low frequency (7 Hz, 0.1 msec, 4-8 V) was not altered by rolipram. Rolipram was without effect on the photic driving response to flash light (2 Hz) in the occipital cortex. Rolipram caused a slight increase in the duration of after discharges induced by electrical stimulation (50 Hz, 0.5 msec, 4-20 V) of the dorsal hippocampus. These results suggest that rolipram is a drug that causes the EEG arousal pattern.