EXPRESSION OF BOMBESIN-RECEPTOR SUBTYPES AND THEIR DIFFERENTIAL REGULATION OF COLONIC SMOOTH-MUSCLE CONTRACTION

Background: Bombesin-related peptides show different potencies, suggesting the existence of at least two receptor subtypes. The aim of this study was to assess the relationship and contribution of each receptor subtype on smooth muscle contraction. Methods: The expression of bombesin-receptor subtype messenger RNA (mRNA) was examined in human and rabbit smooth muscle from the rectosigmoid colon, and the contribution of each of the receptor subtypes to smooth muscle contraction was investigated by blocking mRNA translation of either neuromedin B or gastrin-releasing peptide (GRP) receptor subtype or of both. Results: Neuromedin B and GRP receptor mRNAs were detected in human and rabbit colonic smooth muscle cells. Incubation with neuromedin B receptor antisense oligonucleotides inhibited the neuromedin B-induced contraction, whereas incubation with GRP receptor antisense oligonucleotides inhibited the GRP-induced contraction. Incubation with GRP plus neuromedin B receptor antisense oligonucleotides inhibited the contractile response induced by bombesin, neuromedin B, and GRP. Conclusions: Distinct neuromedin B and GRP receptor subtypes are present on smooth muscle cells of the rectosigmoid colon, and bombesin interacts with both neuromedin B and GRP receptors, resulting in a complex contraction that is sustained in nature. © 1993.