Grass carp somatolactin: II. Pharmacological study on postreceptor signaling mechanisms for PACAP-induced somatolactin-alpha and -beta gene expression.
Somatolactin (SL), the latest member of the growth hormone/prolactin family, is a novel pituitary hormone with diverse functions. However, the signal transduction mechanisms responsible for SL expression are still largely unknown. Using grass carp as an animal model, we examined the direct effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on SL gene expression at the pituitary level. In primary cultures of grass carp pituitary cells, SLalpha and SLbeta mRNA levels could be elevated by PACAP via activation of PAC-I receptors. With the use of a pharmacological approach, the AC/cAMP/PKA and PLC/inositol 1,4,5-trisphosphate (IP(3))/PKC pathways and subsequent activation of the Ca(2+)/calmodulin (CaM)/CaMK-II cascades were shown to be involved in PACAP-induced SLalpha mRNA expression. Apparently, the downstream Ca(2+)/CaM-dependent cascades were triggered by extracellular Ca(2+) ([Ca(2+)](e)) entry via L-type voltage-sensitive Ca(2+) channels (VSCC) and Ca(2+) release from IP(3)-sensitive intracellular Ca(2+) stores. In addition, the VSCC component could be activated by cAMP/PKA- and PLC/PKC-dependent mechanisms. Similar postreceptor signaling cascades were also observed for PACAP-induced SLbeta mRNA expression, except that [Ca(2+)](e) entry through VSCC, PKC coupling to PLC, and subsequent activation of CaMK-II were not involved. These findings, taken together, provide evidence for the first time that PACAP can induce SLalpha and SLbeta gene expression in fish model via PAC-I receptors through differential coupling to overlapping and yet distinct signaling pathways.
Endocrinology Division, School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong SAR, P.R. China.
Quan
Q
Jiang
Mulan
M
He
Xinyan
X
Wang
Anderson O L
AO
Wong
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002347:Carps / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D029941:Fish Proteins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D010902:Pituitary Gland / Q000201:enzymology / Q000502:physiology*; D010907:Pituitary Hormones / Q000096:biosynthesis* / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D002147:Calmodulin; D004791:Enzyme Inhibitors; D029941:Fish Proteins; D006023:Glycoproteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010907:Pituitary Hormones; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; C064448:somatolactin protein, fish; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D002118:Calcium