Guanine nucleotides preferentially inhibit binding of antagonists (male) and agonists (female) to muscarinic receptors of rat adenohypophysis

The effects of guanine nucleotides on the binding properties of muscarinic receptors for muscarinic ligands were studied in male and female rat adenohypophysis preparation, using direct ligand binding with [³H]-N-methyl-4-piperidylbenzilate and by competition with oxotremorine. GTP and Gpp[NH]p (100μM) decreased antagonist binding sites in the male, while those of the female were unaltered. Nucleotide effect on agonist binding was seen only in the female rat, where it stemmed mainly from conversion of high affinity to low affinity binding sites in the diestrous and proestrous stages, while at the estrous stage the opposite effect, i.e. conversion of low to high affinity state, was unexpectedly observed. Sex dimorphism as well as the physiological role of muscarinic receptors in the pituitary are discussed.