Bombesin does not stimulate pepsinogen release in isolated gastric chief cells.
Bombesin (BN)-related peptides, such as gastrin-releasing peptide (GRP), have been shown in vivo to stimulate release of pepsinogen. However, whether this is due to a direct interaction with chief cells is not clear. To clarify this we prepared isolated chief cells (> 90% pure) from guinea pig stomach. BN, GRP, or neuromedin B (NMB), at concentrations up to 1 microM, did not stimulate pepsinogen release or affect the stimulation caused by vasoactive intestinal peptide (VIP) (100 nM) or CCK-8 (10 nM), respectively. In addition, BN, GRP, or NMB at a concentration of 1 microM did not increase cAMP nor did they alter the increase in cAMP caused by VIP or secretin. BN (1 microM) did not alter basal cytosolic calcium [Ca2+]i or affect the increase in [Ca2+]i caused by CCK-8 (1 microM). Furthermore, BN, GRP, or NMB at a concentration of 1 microM did not increase the generation of inositol phosphates (IP) or alter the increase in [3H]IP1, [3H]IP2, or [3H]IP3, caused by CCK-8 (1 microM) or carbachol (1 mM). Binding studies demonstrated no saturable binding of either [125I][Tyr4]BN or [125I][D-Tyr0]NMB using experimental conditions where binding with other peptide ligands to other receptors on chief cells is seen. We conclude that BN-related peptides do not interact directly with specific receptors on chief cells to stimulate or alter stimulated pepsinogen secretion, increase the breakdown of inositol phosphates, or alter [Ca2+]i or cAMP.
Felley
C P
CP
National Institute of Diabetes and Digestive and Kidney Diseases, Digestive Diseases Branch, National Institutes of Health, Bethesda, MD 20892-1804, USA.
Lin
J T
JT
Mantey
S A
SA
Pradhan
T K
TK
Benya
R V
RV
Jensen
R T
RT
D000704:Analysis of Variance; D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010435:Pepsinogens / Q000378:metabolism*; D011869:Radioligand Assay; D018004:Receptors, Bombesin / Q000378:metabolism*; D013268:Stimulation, Chemical
D010435:Pepsinogens; D018004:Receptors, Bombesin; D001839:Bombesin