NEUROPHYSIN EXPRESSION IS STIMULATED BY DOPAMINE D-1 AGONIST IN DISPERSED HYPOTHALAMIC CULTURES

We have exposed primary dispersed hypothalamic cultures from 14-day-ol d fetal Sprague-Dawley rats to substances known to either elevate aden osine 3',5'-cyclic monophosphate (cAMP) levels or increase vasopressin (VP) secretion. The levels of VP in the medium collected from the cul tures were determined by radioimmunoassay, and the number of neurophys in (NP)-positive cells after immunohistochemistry was counted. cAMP-el evating agents, 3-isobutyl-1-methylxanthine (200 mu M) and forskolin ( 25 mu M), in combination (I-F) maintained NP synthesis and VP secretio n in 19-day cultures. I-F replacement by K+ (28 mM), isoproterenol (10 mu M), glutamate (10 mu M), or bicuculline (10 mu M) during the last week of culture resulted in maintenance of NP expression and transient stimulation of VP secretion, but these agents did not induce NP expre ssion independently of I-F treatment. In contrast, exposure to the dop amine D-1 agonist SKF-38393 (10 mu M) significantly increased NP expre ssion independently and after replacement of I-F. Dopamine D-1A recept ors were detected by immunofluorescence on NP-expressing cells, provid ing a morphological basis for this response. These results suggest a r ole for D-1A receptors in the regulation of VP gene expression.