piperidines and decamethonium

This report documents slow changes in cochlear responses produced by electrical stimulation of the olivocochlear bundle (OCB), which provides efferent innervation to the hair cells of the cochlea. These slow changes have time constants of 25-50 sec, three orders of magnitude slower than those reported previously. Such "slow effects" are similar to classically described "fast effects" in that (1) they comprise a suppression of the compound action potential (CAP) of the auditory nerve mirrored by an enhancement of the cochlear microphonic potential (CM) generated largely by the outer hair cells; (2) the magnitude of suppression decreases as the intensity of the acoustic stimulus increases; (3) they share the same dependence on OCB stimulation rate; (4) both are extinguished upon cutting the OCB; and (5) both are blocked with similar concentrations of a variety of cholinergic antagonists as well as with strychnine and bicuculline. These observations suggest that both fast and slow effects are mediated by the same receptor and are produced by conductance changes in outer hair cells. Slow effects differ from fast effects in that (1) fast effects are greatest for acoustic stimulus frequencies between 6 and 10 kHz, whereas slow effects peak for frequencies from 12 to 16 kHz, and (2) fast effects persist over long periods of OCB stimulation, whereas slow effects diminish after 60 sec of stimulation. The time course of the slow effects can be described mathematically by assuming that each shock-burst produces, in addition to a fast effect, a small decrease in CAP amplitude that decays exponentially with a time constant that is long relative to the intershock interval. The long time constant of the slow effect compared to the fast effect suggests that it may arise from a distinct intracellular mechanism, possibly mediated by second-messenger systems.

Topics: Acoustic Stimulation; Animals; Atropine; Bicuculline; Cochlea; Decamethonium Compounds; Dose-Response Relationship, Drug; Efferent Pathways; Electric Stimulation; Guinea Pigs; Hair Cells, Auditory, Outer; Hexamethonium; Membrane Potentials; Models, Neurological; Nerve Fibers; Piperidines; Strychnine; Time Factors; Vestibulocochlear Nerve

Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.

Topics: Anabasine; Androstenedione; Aromatase Inhibitors; Carbachol; Cells, Cultured; Choriocarcinoma; Cotinine; Decamethonium Compounds; Dose-Response Relationship, Drug; Estradiol; Female; Hexamethonium Compounds; Humans; In Vitro Techniques; Kinetics; Microsomes; Nicotine; Piperidines; Placenta; Pregnancy; Pyrrolidinones; Smoking; Succinylcholine; Trophoblasts; Uterine Neoplasms

Topics: Decamethonium Compounds; Muscle Relaxants, Central; Piperidines

Topics: Decamethonium Compounds; Muscle Relaxants, Central; Piperidines