Pharmacology and neurochemistry of bombesin-like peptides.
The pharmacology and neurochemistry of bombesin-like peptides was investigated. Synthetic analogues which had modifications near the N-terminal inhibited specific binding of (125I-Tyr4)BN with high affinity in rat brain and these peptides were potent hypothermic agents after central injection. In comparison, BN-like peptides with modifications near the C-terminal bound with low affinity and were not potent hypothermic agents. These data indicate that the C-terminal of BN is required for central high affinity binding and biological potency. Because substitution of D for L-amino acids at the 8, 10, 13 or 14 positions greatly reduced receptor binding affinity and ability to induce hypothermia, central receptors for BN show marked stereospecificity. Also, the pharmacology of BN in the periphery was investigated using dispersed guinea pig pancreatic acini and found to be similar to that of the brain. Because endogenous BN-like peptides extracted from brain tissue possess appreciable biological activity, these receptors are likely activated by endogenous BN-like peptides in vivo.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001839:Bombesin / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D001923:Brain Chemistry; D006168:Guinea Pigs; D008297:Male; D010179:Pancreas / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010455:Peptides; D000681:Amylases; D001839:Bombesin