Ca2+-dependent and -independent secretagogue action on gastric mucus secretion in rabbit mucosal explants

Am J Physiol. 1989 Apr;256(4 Pt 1):G739-46. doi: 10.1152/ajpgi.1989.256.4.G739.

Abstract

The secretion of high-molecular weight glycoprotein was studied in rabbit antral and fundic explants in response to acetylcholine (ACh), the calcium ionophore A23187, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), forskolin, histamine, pentagastrin, and prostaglandin E2 (PGE2). Glycoprotein secretion was measured in pulse-chase experiments by incorporation of [14C]N-acetyl-D-glucosamine into explants and quantification of the secreted high-molecular weight-labeled glycoprotein. All tested agents except histamine and pentagastrin stimulated glycoprotein secretion in a concentration-dependent manner. The response to A23187 was abolished by removal of extracellular Ca2+ and greatly reduced by the calmodulin antagonist N-(6-amino-hexyl)-l-naphthalenesulfonamide (W7). The response to ACh was abolished by equimolar concentrations of atropine and by depletion of intracellular Ca2+ stores, an effect which was reversible on addition of Ca2+, and reduced by W7. The response to forskolin and PGE2 was not significantly affected by either extracellular or intracellular Ca2+ depletion. The combination of ACh with forskolin and A23187 with TPA had a synergistic effect on secretion. The absolute dependence of cholinergic stimulation on the presence of intracellular Ca2+ and the Ca2+-independent stimulatory effect of forskolin and PGE2 suggest that gastric mucus secretion can be elicited by at least two distinct pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Acetylglucosamine / metabolism
  • Animals
  • Atropine / pharmacology
  • Calcimycin / pharmacology
  • Calcium / pharmacology*
  • Calmodulin / antagonists & inhibitors
  • Colforsin / pharmacology
  • Dinoprostone / pharmacology
  • Gastric Fundus / metabolism
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism*
  • Glycoproteins / metabolism*
  • Histamine / pharmacology
  • Male
  • Molecular Weight
  • Organ Culture Techniques
  • Pentagastrin / pharmacology
  • Pyloric Antrum / metabolism
  • Rabbits
  • Sulfonamides / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Calmodulin
  • Glycoproteins
  • Sulfonamides
  • Colforsin
  • Calcimycin
  • W 7
  • Atropine
  • Histamine
  • Pentagastrin
  • Dinoprostone
  • Acetylcholine
  • Tetradecanoylphorbol Acetate
  • Calcium
  • Acetylglucosamine