The overall objective of this work is to elucidate the autonomic regulation of human labial gland function. This proposal concentrates on characterizing the autonomic receptors present in the gland, and on documenting some of the biochemical and physiological responses evoked by receptor activation. The biochemical responses of present interest involve changes in gland cyclic nucleotide concentrations, while the physiological responses involve activation of cell K release.
The specific aims are as follows:
Specific Aim 1. To show that labial glands possess normal numbers of muscarinic cholinergic and beta-adrenergic receptors, and relatively low numbers of alpha-adrenergic receptors.
Specific Aim 2. To determine the binding affinities of these receptors for the corresponding agonists and antagonists, and to obtain information regarding the receptor subtypes.
Specific Aim 3. To characterize the biochemical and physiological effects of autonomic receptor activation in labial glands.
The specific aims dealing with numbers of receptors and receptor binding affinities will be accomplished using a labial gland membrane preparation that will be incubated with appropriate radioligands in the presence or absence of various antagonists.
The specific aim dealing with biochemical and physiological effects of autonomic receptor activation will involve incubating labial gland slices in vitro, and measuring receptor induced changes in gland cyclic nucleotide concentrations, or receptor induced activation of gland K release, a measure of gland electrolyte and, presumably, gland fluid secretion. Preliminary results are presented for all aspects of the work and show that the proposed experiments are feasible for labial gland samples. Completion of this work will lead to a significant increase in our knowledge of the normal autonomic regulation of human labial gland secretory function. The data and procedures developed in this study should find numerous applications in future studies in human salivary gland disease.
