Muscarinic cholinergic receptors have been found to exist on the membranes of anterior pituitary cells. Although the receptors seem to regulate secretion of both prolactin (PRL) and growth hormone (GH), no good evidence is available as to which of the several cell types present in the anterior pituitary has the receptors. Furthermore, there are no data describing the physiological significance of these receptors. This proposal will characterize the muscarinic receptor in the rat anterior pituitary as to: 1) number and location e.g., cell type, 2) physiological significance in controlling GH and PRL secretion; 3) the interplay of various hypothalamic releasing/inhibiting factors. The project will make use of several major types of methodology: The muscarinic receptor population will be studied both on intact cells maintained in culture and on membranes isolated from animals in various physiological states. Use of cell separation technology and electron microscopy will aid in localization of the muscarinic receptors to specific cell types and thus support the localization obtained physiologically via hormone secretion experiments. The effect of interaction of peptides (such as somatostatin, vasoactive intestinal peptide and thyroid stimulating hormone-releasing hormone) found in the hypothalamus and muscarinic receptor agonists (e.g., acetylcholine and oxotremorine) on secretion of hormones and binding to the receptor will be described, then correlated, in an effort to define the physiological relevance of the muscarinic receptor to regulation of GH and PRL secretion. The results of these studies may provide new possibilities for pharmacological control of anterior pituitary hormones, especially GH and PRL.
