PHARMACOLOGICAL STUDIES OF CENTRAL SYNAPTIC TRANSMISSION

Summary

Principal Investigator: SOLOMON ERULKAR
Abstract: Our experiments have shown that myotubes derived from laryngeal muscles of adult male Xenopus laevis can be grown in culture and that they contain androgen receptors similarly to their adult counterparts. By the use of patch clamp techniques, we have shown that 5-alpha-dihydrotestosterone (5 alpha-DHT) added to the bath can induce: 1) "anesthetic-like" effects at Acetylcholine (ACh)-activated single channels after exposure to the steroid for short periods (less than 10 minutes), and 2) changes in the properties and number of ACh-receptors after exposure to the steroid in the culture medium for periods over six days. We believe that this latter effect occurs through genomic mechanisms. We have also shown the existence at the membranes of these myotubes of a high-conductance (400pS), voltage-dependent population of channels in the absence of exogenous neurotransmitter or steroid. We now intend a) to determine the ionic selectivity of these high-conductance channels, and b) to compare the anesthetic-like effects at ACh-activated single channels with those of known steroid anesthetics that are not hormonal. The main thrust of our research, however, will be to test the hypothesis suggested from our previous work and from studies by other authors, using other approaches, that the gonadal steroids act to change the properties and numbers of neurotransmitter receptors at all excitable cells that contain the steroid receptors. We shall, therefore, study: a) the properties of single channels activated by adrenergic agonists of membranes of myometrial cells isolated from uterus of female rats at different hormonal states. The effects of the hormones on both alpha-and beta-adrenoceptors will be tested; b) the effects of both male and female hormones on GABA-activated single channels of central neurons isolated in culture from defined regions of the central nervous system of adult male and female Xenopus laevis. The results of these experiments will form a beginning for future studies on the effects of steroid hormones on other neurotransmitter receptors at other excitable cells. If the hypothesis holds true for the cells tested, it would strongly suggest that the gonadal steroids play a major role in the modulation and regulation of neuronal and muscular activity.
Funding Period: 1978-07-01 - 1992-06-30
more information: NIH RePORT