A. Molecular characterization of NMB and GRP receptors. 1. We demonstrated that multiple serines and threonines located within the carboxyl terminus of the GRP receptor (GRP-R) distal to Cys341, including but limited to those within the PKC consensus, specifically regulate GRP-R internalization. 2. In collaboration with J. Battey (NCI) we demonstrated that the Ile216 of the 5th transmembrane area of the NMB-R is critically important for determining selective high affinity NMB-R binding. B. Molecular characterization for the CCK-gastrin related peptides. 1. Cloning of human CCKA and CCKB receptors. Both the human CCKA and CCKB receptors were cloned for the first time. 2. Mapping of CCKAand CCKBreceptors in rat brain. Using 35S- labeled cRNA antisense probes the expression of CCKA and CCKB receptors was mapped for the first time. 3. Characterization of CCKA receptors in gallbladder and pancreas. The CCKA receptors from GB and pancreas were cloned from guinea pig and shown to be identical. These results do not support a previous proposal that they might represent different subtypes based on binding studies. C. Molecular characterization of PACAP-receptors. For the first time the specific high affinity receptor for PACAP was cloned and expressed.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Igarashi, Hisato; Ito, Tetsuhide; Hou, Wei et al. (2002) Elucidation of vasoactive intestinal peptide pharmacophore for VPAC(1) receptors in human, rat, and guinea pig. J Pharmacol Exp Ther 301:37-50
Ito, T; Igarashi, H; Pradhan, T K et al. (2001) GI side-effects of a possible therapeutic GRF analogue in monkeys are likely due to VIP receptor agonist activity. Peptides 22:1139-51
Ito, T; Hou, W; Katsuno, T et al. (2000) Rat and guinea pig pancreatic acini possess both VIP(1) and VIP(2) receptors, which mediate enzyme secretion. Am J Physiol Gastrointest Liver Physiol 278:G64-74