STIMULATION OF GROWTH-HORMONE RELEASE FROM RAT PRIMARY PITUITARY-CELLS BY L-692,429, A NOVEL NON-PEPTIDYL GH SECRETAGOGUE

L-692,429, a benzolactam derivative, stimulated GH release from rat pr imary pituitary cells in a dose-dependent manner. The concentration of L-692,429 required for half-maximal stimulation were 59.6 +/- 7.3 nM. Under the same conditions, GHRP-6 and GRF had EC50 values of 10.3 +/- 1.9 nM and 0.47 +/- 0.09 nM, respectively. L-692,428, the enantiomer of L-692,429, was inactive at a concentration as high as 2 muM. Like G HRP-6, L-692,429 had no effect on intracellular cAMP level; however, i t synergized with GRF to further increase not only the accumulation of cAMP but also the release of GH. The magnitude of GH release stimulat ed by maximal concentrations of L-692,429 and GHRP-6 was comparable. I nterestingly, when presented together in maximal concentrations, L-692 ,429 and GHRP-6 did not cause additional GH release when compared with either secretagogue alone. The L-692,429-stimulated GH release was co mpletely inhibited by 20 nM somatostatin. To our knowledge, L-692,429 is the first non-peptidyl GH secretagogue which has a direct effect on the release of growth hormone from rat primary pituitary cells. Its e ffect is most likely mediated through a mechanism which is similar to that of GHRP-6.