PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP)-38 AND PACAP27 ACTIVATE COMMON AND DISTINCT INTRACELLULAR SIGNALING PATHWAYS TO STIMULATE GROWTH-HORMONE SECRETION FROM PORCINE SOMATOTROPES

We have recently shown that the two bioactive forms of pituitary adeny late cyclase-activating polypeptide, PACAP38 and PACAP27, stimulate GH release and GH messenger RNA (mRNA) accumulation in cultured porcine pituitary cells. However, dose- and time-related differences in the re sponse to both peptides suggested that the signaling mechanisms activa ted by PACAP38 and PACAP27 in this cell type could differ. To test thi s hypothesis, we have evaluated hormone release and GH mRNA content af ter PACAP treatment in combination with selective activators and inhib itors of the adenylate cyclase/ cAMP/protein kinase A and the phosphol ipase C/inositol phosphate (IP)/protein kinase C pathways, and with bl ockers of intra- and extracellular Ca2+. Our results show that activat ion of the adenylate cyclase/cAMP/protein kinase A system, and extrace llular Ca2+ entry through L-type Ca2+-channels are prevailing and requ isite signals for the transduction of the stimulatory effects of both PACAP38 and PACAP27 on GH release and transcription in porcine somatot ropes. However, phospholipase C and intracellular Ca2+ also contribute , although partially, to PACAP38-induced, but not to PACAP27-induced i ncrease in porcine GH secretion and mRNA levels. These findings demons trate that in normal somatotropes, PACAF38 can activate multiple trans duction pathways that differ from those employed by PACAP27. Moreover, these differences could account for the previously described divergen ces in the actions of either peptide in porcine somatotropes.