PACAP hybrid: a new PACAP receptor antagonist.
The effects of pituitary adenylate cyclase activating polypeptide (PACAP) hybrid, a synthetic antagonist, was investigated on NIH/3T3 cells containing PACAP receptor (R) splice variants (SVs). PACAPhybrid inhibited 125I-PACAP-27 binding to NIH/3T3 cells stably expressing PACAP-R basic, SV-1, SV-2 or SV-3 with an IC50 of 1000 nM. PACAPhybrid antagonized the ability of PACAP-27 to elevate cAMP regardless of the PACAP-R SV used. PACAP was more efficacious at increasing cytosolic Ca2+ in NIH/3T3 cells containing PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in cytosolic Ca2+ caused by PACAP-27 regardless of the PACAP-R SV used. PACAP was more potent at elevating c-fos mRNA using NIH/3T3 cells transfected with PACAP-R SV-2 than PACAP-R basic, SV-1 or SV-3. PACAPhybrid antagonized the increase in c-fos mRNA caused by PACAP-27. These data suggest that PACAPhybrid is a useful PACAP receptor antagonist for PACAP-R SVs.
Pisegna
J R
JR
CURE: VA/UCLA, Digestive Diseases Center, West L.A. VA Medical Center, CA 90073, USA.
Leyton
J
J
Coelho
T
T
Hida
T
T
Jakowlew
S
S
Birrer
M
M
Fridkin
M
M
Gozes
I
I
Moody
T W
TW
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016762:Genes, fos; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D017385:Sequence Homology; D014162:Transfection
C495401:ADCYAP1 protein, human; C495402:Adcyap1 protein, mouse; D007457:Iodine Radioisotopes; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone