Actions of gastrin-releasing peptide and related mammalian and amphibian peptides on ion transport in the porcine proximal jejunum.
The 27-amino acid peptide gastrin-releasing peptide (GRP) and the decapeptide neuromedin B (NMB) are structurally related to bombesin (BB) and exist within the mammalian small intestine. We examined the actions of porcine GRP and NMB on ion transport in the porcine proximal jejunum in vitro and compared their activities to those of their respective C-terminal amphibian homologs BB and ranatensin (RT). The 4 peptides transiently increased potential difference and short-circuit current (Isc) in jejunal mucosal sheets after their serosal administration in subnanomolar concentrations with an order of potency: GRP approximately RT greater than or equal to NMB greater than BB. BB and RT were more effective in elevating Isc than GRP and NMB; all peptides had variable effects on tissue conductance. Mucosal Isc responses to GRP (1 nM) were due in part to a stimulation of net Cl- secretion. GRP-induced Isc increases were halved by serosal furosemide (0.3 mM) and reduced by 65% and 90% in tissue bathing solutions lacking Cl- or Cl- and HCO3-, respectively. Tetrodotoxin reduced Isc responses to the peptide by 40%; GRP activity remained unaffected after blockade of gut muscarinic or nicotinic cholinergic receptors by atropine or hexamethonium, respectively. These results suggest that GRP and its natural homologs stimulate active electrogenic Cl- secretion in the porcine jejunum through interactions with GRP receptors located in the intestinal mucosa and submucosa.
Chandan
R
R
Department of Veterinary Biology, University of Minnesota, College of Veterinary Medicine, St. Paul 55108.
Newell
S M
SM
Brown
D R
DR
D000663:Amphibians; D000818:Animals; D000838:Anions; D001692:Biological Transport / Q000187:drug effects; D004553:Electric Conductivity; D019886:Gastrin-Releasing Peptide; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D013552:Swine
D000838:Anions; D005768:Gastrointestinal Hormones; D010455:Peptides; D019886:Gastrin-Releasing Peptide