Guanyl nucleotides participate in the beta-adrenergic stimulation of adenylate cyclase activity in the intermediate lobe of the rat pituitary gland.

The existence of a stimulatory guanyl nucleotide component in the intermediate lobe of the rat pituitary gland (IL) is supported by the observations that: 1) GTP was required for beta-adrenergic stimulation of adenylate cyclase activity in homogenates of IL tissue; 2) GTP, in the absence of a beta-adrenergic agonist, maximally stimulated adenylate cyclase activity in homogenates of IL tissue previously treated with cholera toxin; and 3) GTP decreased the affinity of the beta-adrenoceptor for isoproterenol, a beta-adrenergic agonist. Although when tested on fresh IL tissue, 5'-guanylyl imidodiphosphate [Gpp(NH)p], a nonhydrolyzable analog of GTP, was substantially less active than GTP in stimulating adenylate cyclase activity in the presence of isoproterenol, GTP and Gpp(NH)p each stimulated adenylate cyclase to the same degree after solubilization of IL tissue previously treated with cholera toxin. GTP and Gpp(NH)p appeared to interact at the same site in this preparation.