Corticostatic Peptides Cause Nifedipine-Sensitive Volume Reduction in Jejunal Villus Enterocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1991-01, Vol.88 (2), p.552-556
• Main Authors: MacLeod, R. John, Hamilton, J. R., Bateman, A., Bellcourt, D., Hu, J., Bennett, H. P. J., Solomon, S.
• Format: Article
• Language: English
• Subjects: activation; Amino Acid Sequence; Animals; Calcimycin - pharmacology; calcium; Cell physiology; cell volume; changes; Channel blockers; Chemical suspensions; chloride; conductance; corticostatin; Crypts; defensin; Enterocytes; Epithelial cells; Epithelium - drug effects; Epithelium - physiology; Gramicidin - pharmacology; Guinea Pigs; Humans; In Vitro Techniques; Jejunum; Jejunum - drug effects; Jejunum - physiology; Kinetics; like; Medical sciences; Molecular Sequence Data; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; nifedipine; Nifedipine - pharmacology; peptides; Peptides - isolation & purification; Peptides - pharmacology; Phagocytes; Physiological stimulation; potassium; Quinine - pharmacology; sensitivity; Sequence Homology, Nucleic Acid; Sodium - pharmacology; Structure-Activity Relationship
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.2.552

We studied cell-volume changes caused by adding corticostatin (CS) or defensin-like peptides to villus enterocytes isolated in suspension from guinea pig jejunum. Guinea pig CS (10-9M) added to villus cells in Na+-containing medium reduced volume, but immediate cell swelling was caused by 10-6M guinea pig CS. In Na+-free N-methyl-D-glucamine-containing medium 10-9M guinea pig CS accelerated the initial rate of shrinkage compared with cells in N-methyl-D-glucamine-containing medium alone as well as causing greater cell shrinkage. Guinea pig CS-stimulated cell shrinkage was prevented by a Ca2+-channel blocker-5 μ M nifedipine, by chelation of extracellular Ca2+with 100 μ M EGTA, or by ω-conotoxin (10-9M). The Ca2+ionophore A23187 (2.5 μ M) reduced volume when added to villus cells in N-methyl-D-glucamine-containing medium; this action was prevented by EGTA, or quinine-an inhibitor of K+conductance, or 9-anthracenecarboxylic acid-a Cl-channel blocker, suggesting that the volume reduction occurred because K+and Cl-conductances were activated. Guinea pig CS-stimulated volume reduction was also prevented by 100 μ M quinine or 9-anthracenecarboxylic acid. We conclude that jejunal villus enterocytes possess a Ca2+-activated Cl-conductance and a K+conductance that need not be stretch-activated. Corticostatic peptides cause volume reduction in villus cells by activating L-type Ca2+channels; other defensin-like peptides were without effect.