Structure-activity requirements of bombesin for gastrin-releasing peptide- and neuromedin B-preferring bombesin receptors in rat brain.

The pharmacological profile of [125I][Tyr4]bombesin binding to gastrin-releasing peptide- and neuromedin B-preferring sites has been investigated in rat cerebral cortex and olfactory bulb membranes, respectively. [125I][Tyr4]bombesin specific binding to cerebral cortex membranes was displayed biphasically by gastrin releasing peptide and [D-Phe6]bombesin-(6-13)-ethyl amide. In the presence of 10 mM neuromedin B, displacement curves for bombesin-related peptides were monophasic with gastrin releasing peptide displaying approximately 100-fold higher affinity than neuromedin B. In olfactory bulb membranes, [125I][Tyr4]bombesin binding was also displaced biphasically by gastrin releasing peptide, [D-Phe6]bombesin-(6-13)-ethyl amide and neuromedin B. In the presence of 10 microM [D-Phe6]bombesin-(6-13)-ethyl ester, displacement curves were monophasic with neuromedin B possessing approximately 10-fold higher affinity than gastrin-releasing peptide. Under these conditions, successive deletion of N-terminal amino acids from bombesin-(1-14) was well tolerated at both sites, with little loss in affinity up to bombesin-(5-14). A 5- to 10-fold drop in affinity was observed at both sites with bombesin-(6-14), whilst the octapeptide acetyl-bombesin-(7-14) displayed similar affinities to bombesin-(1-14). Bombesin-(8-14), -(9-14) and -(10-14) were essentially inactive (IC50 > 10 microM). C-terminal deletion of Met24 (bombesin-(1-13)) resulted in 100-fold loss of affinity at the gastrin-releasing peptide site and complete loss of affinity at the neuromedin B site. Fragments smaller than bombesin-(1-13) were virtually inactive at either site.(ABSTRACT TRUNCATED AT 250 WORDS)