CATECHOLAMINE/OPIOID CONTROL OF VISCERAL REFLEXES IN NTS

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Catecholamines and opiates potently modulate baro- and chemosensory reflexes attributed to the release of L-glutamate and/or substance P from visceral afferents that terminate mainly in the medial (m) and commissural (com) nuclei of the solitary tract (NTS). The director of the modulation is dependent on the receptor subtype, location, and association with N-methyl-d-aspartate (NMDA) and non-NMDA type glutamate receptors. In this project, these functional sites will be examined in three interrelated studies using electron microscopic (EM) immunocytochemistry for the localization of antipeptide antisera against catecholamine, opioid, and glutamate receptors in the mNTS and comNTS of the rat brain. Study I will test the hypotheses that in these regions, alpha2A - adrenergic receptors (alphs2A -AR) and D2 -dopaminergic receptors (D-R) are localized to (I) sites involved in storage or release of their respective catecholamines, consistent with involvement in autoregulation, or (ii) baro- or chemosensory afferents or their targets, indicating the most probable sites for direct modulation of cardiorespiratory reflexes. Study II will test the hypotheses that mu-opioid receptors (MOR) and/or sigma-opioid receptors (DOR) in the NTS are localized to (I) pre- or postsynaptic sites on neurons containing endogenous opioid peptides, catecholamines, and/or alpha2A -AR, suggesting sites for opioid autoregulation and for functional interactions with catecholamines, (ii) baro- or chemosensory afferents, or substance P containing terminals, suggesting involvement in the presynaptic release of excitatory neurotransmitters, or (iii) second order sensory neurons, suggesting involvement in postsynaptic responses to peripheral excitation. Study III will test the hypothesis that kainate receptors and NMDA receptors are differentially distributed with respect to each other, and to neurons expressing alpha2A -AR or MOR, suggesting that catecholamine and/or opioid modulation may at least partially depend on the presence of a specific excitatory amino acid receptor. Other specific aims of this study are to determine whether kainate or NMDA receptors are present on (I) baro- or chemosensory afferents, suggesting sites for autoregulation of glutamate release, or (ii) second-order sensory neurons, suggesting involvement in glutamatergic excitation. Together, the results will have direct relevance to understanding the pathophysiology of, and devising new treatments for, hypertension, somato-sympathetic pain, and ischemic brain damage associated with reflex changes in cerebral blood flow.