Pituitary adenylate cyclase activating polypeptide (PACAP38) stimulated growth hormone release as well as cAMP accumulation in a static rat primary pituitary cell culture in a dose-dependent manner with EC50 values of 1.9 +/- 0.4 nM (n = 13) and 0.9 +/- 0.3 nM (n = 5), respectively. The maximal GH response was observed between 5 to 15 min. Prolonged incubation (3 to 4 hrs) markedly reduced the stimulatory effect of PACAP38. The effect of PACAP38 on GH release was desensitized by pretreatment of the cells with PACAP38 or GRF, but not with PMA. The PACAP38-induced desensitization appeared to be time- and dose-dependent. Somatostatin (20 nM) inhibited PACAP-stimulated GH release through a cAMP-independent pathway.