Abstract

Receptors for the bombesin family of peptides are present on human and guinea pig respiratory tract submucosal glands and mediate glandular exocytosis. The effects of gastrin releasing peptide (GRP), neuromedin B (NMB), the amphibian skin peptides ranatensin and phyllolitorin and bombesin antagonists were assessed in the guinea pig nasal mucosal secretion model vivo, GRP induced significant total protein and alkaline phosphatase secretion with half maximal responses at 1 and 10 nM, respectively. NMB induced a larger percent change in alkaline phosphatase secretion than GRP with a half maximal response at less than 1 nM NMB. GRP-induced secretion was antagonized by three bombesin-like peptide analogs: BIM-26028, BIM-26187 and BIM-26226. Total protein secretion induced by 100 nM GRP was reduced 50% by BIM-compounds at concentrations of 1 to 3 nM, although BIM-26226 was even more potent on alkaline phosphatase secretion. BIM-26226 (1 nM) reduced the effects of increasing doses of GRP and NMB, Ranatensin and phyllolitorin did not stimulate any secretion. mRNA for GRP receptors, NMB receptors, bombesin receptor subtype 3, GRP and NMB were detectable in human nasal mucosal samples. These and previous data suggest that: 1) GRP is a more potent secretagogue of total protein than NMB and bombesin, 2) NMB is more potent at stimulating alkaline phosphatase, 3) ranatensin and phyllolitorin are not secretagogues, 4) BIM-26226 is a potent GRP and NMB antagonist, 5) these compounds do not alter basal secretion, suggesting that GRP and NMB do not play active roles stimulating tonic secretion in this model and 6) GRP, and potentially NMB, released from nerves or other sites may act on GRP receptor, NMB receptor or bombesin receptor subtype 3 to induce glandular secretion in respiratory mucosa.