Suppression of the nicotinic acetylcholine response in rat superior cervical ganglionic neurons by steroids.

The effects of various types of steroids on the nicotinic acetylcholine (ACh) receptor (nAChR)-mediated responses were investigated in superior cervical ganglionic neurons acutely dissociated from rats using nystatin perforated patch recording. ACh induced a peak followed by a gradual decrease in the inward current at a holding potential of -40 mV. Nicotine, but not muscarine, mimicked ACh. Hydrocortisone at a concentration of >10(-6) M reversibly suppressed both the peak and steady-state nicotine-induced currents (Inic) in a noncompetitive manner. The inhibition of Inic by hydrocortisone did not show any voltage dependency and persisted in the presence of either cyclic AMP modulators, forskolin and 3-isobutyl-1-methylxanthine, or a protein kinase A inhibitor, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89). Beta-estradiol, androsterone, aldosterone, and 17alpha-estradiol mimicked hydrocortisone in its inhibitory action on ACh-induced currents (I(ACh)). The potency for the inhibitory actions on I(ACh) was as follows: androsterone > beta-estradiol > hydrocortisone > or = aldosterone = 17alpha-estradiol. Cholesterol had no effect on the I(ACh). In conclusion, the structural characteristics of a steroid are thus considered to be necessary to block nicotinic I(ACh) in rat superior cervical ganglionic cells, whereas the cholesterol side chain might disturb the inhibitory action of the steroid skeleton on nAChRs.

Modulation of serotonin-induced currents by metals in mouse neuroblastoma cells.

The effects of several metals on the serotonin receptor-channel complex were studied using mouse neuroblastoma N1E-115 cells which are known to be endowed with the 5-HT3 subclass of the receptor. The whole-cell patch clamp technique was used to record currents induced by serotonin at a concentration of 3 microM which was equivalent to the apparent dissociation constant. Methylmercury and mercuric chloride suppressed serotonin-induced currents irreversibly, with a 50% suppression being observed at concentrations of 3 microM and 2 microM, respectively. Lead and zinc suppressed the current with IC50S of 80 microM and 50 microM, respectively, and the effects of both metals were reversible after washing with metal-free solution. Lanthanum also suppressed the current with an IC50 of 10 microM, and the effect was partially reversible. Cadmium and cobalt augmented serotonin-induced currents slightly but consistently at a concentration of 100 microM, and the effect was reversible. Aluminum at 100 microM, had no effect on serotonin-induced currents. It was concluded that the 5-HT3 receptor is endowed with a unique property with respect to the actions of metals which is not shared by some other ligand-gated and voltage-gated ion channels.

Entrainability of circadian activity of the mosquito Culex pipiens pallens to 24-hr temperature cycles, with special reference to involvement of multiple oscillators.

Entrainability of the circadian rhythm of mosquito flight and locomotor activity was investigated by giving a 24-hr temperature cycle (28 degrees C for 16 hr, 23 degrees C for 8 hr) to the free-running rhythm or by shifting the temperature cycle. The phase angle difference between the entrained rhythm and the temperature cycle depended on the free-running period, but not on the circadian phase at which the temperature cycle started. The rhythm transients (advancing or delaying) to entrainment depended on phase, but did not depend on either the phase or the free-running period for their average speed. We postulate that flight and locomotor activity in the mosquito may be controlled by two circadian oscillators moving in different directions in response to the temperature cycle. It is likely that at least one of the oscillators is diphasic.