Characterization of In Vitro Release of Neurochemicals from the Intermediate Area of the Rat Thoracic Spinal Cord: Regulation by Coexisting Neurochemical and Presynaptic Autoreceptors.

摘要

Serotonin (5-HT), substance P (SP), neurokinin A (NKA) and thyrotropin-releasing hormone (TRH) coexist in the ventral medullary neurons which project to theintermediolateral cell column (IML, site of sympathetic preganglionic neurons) of the thoracic spinal cord. It is not known whether these neurochemicals are released from the IML, interact with each other and thus regulate the activities of the sympathetic nervous system. In this thesis, the release of 5-HT, SP and NKA from the microdissected intermediate area (includes the IML) of the rat thoracic spinal cord is investigated using an in vitro superfusion system. Regulation of the release of 5-HT and SP by presynaptic auto receptors and the other coexisting neurochemicals is also studied. Potassium depolarization induces extracellular Ca2+-dependent differential release of [3H]5-HT, SP and NKA from the intermediate area. The release of [3H]5-HT is induced by lower concentrations of K+, while the release of SP and NKA requires higher concentrations of K+. The release of [3H]5-HT is negatively regulated by 5-HT through activation of presynaptic 5-HT18 inhibitory auto receptors and positively regulated by SP through activation of presynaptic NKl autoreceptors. The release of SP, comes at least partly, from serotoninergic nerve terminals, as serotoninergic neurotoxin pretreatment decreased SF content and the absolute amount of SP released from the intermediatearea. However, the release of SP is probably not under the influence of 5-HT because 5-HT and 5-HT agonists failed to change the percentage of fractional release of SP. The release of SP is possibly regulated by presynaptic NKl receptors, as an NKl receptor antagonist (GR 82334) dose-dependently increased the K+-stimulated release of SP. Neither NKA, TRH nor their analogues altered the release of [3H]5-HT or SP.