Characterization of four receptor cDNAs: PAC1, VPAC1, a novel PAC1 and a partial GHRH in zebrafish.
To understand the role of growth hormone-releasing hormone (GHRH) and pituitary adenylate cyclase-activating polypeptide (PACAP) and to examine the functional significance of the co-expression of GHRH and PACAP in fish, their receptors were characterized in zebrafish. Three cDNAs encoding the PAC(1) receptor, the VPAC(1) receptor, and the partial GHRH receptor were identified from zebrafish. Functional expression of the PAC(1) and VPAC(1) receptors revealed that both are potently coupled to the adenylyl cyclase pathway, but only the PAC(1) receptor is coupled to the phospholipase C pathway. Transcripts for all three receptors were widely distributed, often in an overlapping pattern in the adult zebrafish. Also, one splice variant of the partial GHRH receptor and three splice variants of the PAC(1) receptor were identified from adult zebrafish. The long GHRH receptor transcript contained a 27 amino acid insert in transmembrane domain 5 encoding a premature stop codon leading to a truncated receptor protein. For the PAC(1) receptor, two of the splice variants corresponded to the hop1 and hop2 variants characterized in mammals. The third splice variant identified from the gill encoded a novel 107 bp insert containing a premature stop codon. Therefore, PACAP and GHRH have widespread, overlapping target sites suggesting a coordinated role for these hormones in evolution.
Fradinger
Erica A
EA
Department of Biology (EAF, JAT, NMS), University of Victoria, P.O. Box 3020 STN CSC, Victoria, BC, Canada V8W 3N5.
Tello
Javier A
JA
Rivier
Jean E
JE
Sherwood
Nancy M
NM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D018389:Codon, Nonsense; D018076:DNA, Complementary; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics* / Q000502:physiology; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D016415:Sequence Alignment; D014018:Tissue Distribution; D010738:Type C Phospholipases / Q000378:metabolism; D015027:Zebrafish
D018389:Codon, Nonsense; D018076:DNA, Complementary; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D013007:Growth Hormone-Releasing Hormone; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases