Characterization And Pharmacology Of Receptors For Gastrointestinal Peptides

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

During the year the receptor pharmacology and molecular pharmacology of primarily the VIP/PACAP family and bombesin receptor family (GRPR, NMBR, BRS-3) were investigated. Data from our studies as well as from the literature was used to update the IUPHARs (bombesin receptor section, committee Chair-RT Jensen) in its Concise Guide to Pharmacology 2021/2022. In addition, this data was used to review and provide evidence supporting possible therapeutic roles utilizing the ectopic expression of bombesin receptors in CNS/neural tumors to provide novel targeted therapeutic approaches. Furthermore, the receptor pharmacology as well as the signaling for the VIP/PACAP family was reviewed and the recent advances reviewed in possible therapeutic approaches in various human diseases the pathogenesis of headaches (migraine, etc.) as well as posttraumatic stress disorder and drug/alcohol/smoking addiction using both our data and the data from the literature on this receptor family. Receptors for these family of peptides are frequently ectopically overexpressed by using tumors and one of the main effects is that activation of these receptors can transactivate the EGFR family of receptors which can have marked effects on tumor behavior, including increased growth, invasiveness, and migration. This area was generally reviewed for these family of receptors this year as well as a specific study completed reporting showing PAC1 receptor activation by PACAP and related peptides not only can transactivating the EGFR but also other members of the EGFR family such as HER3 and this can have pronounced effects on tumor growth. Detailed studies using receptor chimeras and receptor site-specific mutagenesis are continuing to explore the molecular basis for various ligands recently described for BRS-3 as well as the other two human BN receptors(GRPR, NMBR).