Sensory receptors are categorized as 'primary' receptors (where the sensory ending is excited directly by the stimulus) or 'secondary' receptors (where the transduction of the sensory stimulus requires a pre-neural cell). Secondary receptors thus require electrical or chemical coupling between pre-neural cells and afferent nerve fibers. The carotid body chemoreceptors are considered secondary-type receptors, with chemical sensory synapses thought to exist between pre-neural (type I) cells and sensory terminations of the carotid sinus nerve. Putative neurotransmitters, including biogenic amines (catecholamines and acetylcholine) and neuroactive peptides (enkephalins and substance P) are contained in this receptor and are thought to play a role in the genesis of the chemoresponse. The objectives of this proposal proceed from our previous studies and continue to pivot about a central goal: i.e., to elucidate the mechanisms of sensory transmission and chemotransduction in the carotid body. The following five projects are proposed for the new grant period: Studies on the role of biogenic amines (Project 1) and neuropeptides (Project 2) will characterize the relationship between chemosensory discharge, and synthesis (and/or content), release, and receptor sites of action for these substances. Emphasis will be on studies of co-transmitter interactions and modulation of the sensory synapse. The distribution and co-existence of neuropeptides and enzymes of biogenic amine synthesis (Project 3) will be examined using a novel set of particulate markers in combination with analytical electron microscopy (AEM). Studies on the mechanisms of stimulus transduction (Project 4) will explore the energetic metabolism (2DG, ATP assays) and ionic trigger events (Ca++ entry) associated with the chemoresponse. Finally, our studies of trophic phenomena in secondary sensory receptors (Project 5) will continue with re-innervation experiments which assess the retrograde trophic influence of sensory end-organs on the expression of transmitter specific characteristics in mature sensory neurons. The experiments involved in this multi-disciplinary study require a variety of methods and techniques, including: HPLC and RIA of transmitter substances, radio-labelling of transmitter stores and release, receptor binding, enzyme assays, auto-radiography, immunocytochemistry (LM and AEM), electrophysiological techniques, 2-DG-P and ATP measurements, and LM and EM assessment of trophic phenomena.
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