Corticostatic peptides cause nifedipine-sensitive volume reduction in jejunal villus enterocytes.
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(-9) M) added to villus cells in Na(+)-containing medium reduced volume, but immediate cell swelling was caused by 10(-6) M guinea pig CS. In Na(+)-free N-methyl-D-glucamine-containing medium 10(-9) M 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 microM nifedipine, by chelation of extracellular Ca2+ with 100 microM EGTA, or by omega-conotoxin (10(-9) M). The Ca2+ ionophore A23187 (2.5 microM) 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 microM 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.
Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
R J
RJ
MacLeod
J R
JR
Hamilton
A
A
Bateman
D
D
Belcourt
J
J
Hu
H P
HP
Bennett
S
S
Solomon
D000595:Amino Acid Sequence; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006096:Gramicidin / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007583:Jejunum / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D012964:Sodium / Q000494:pharmacology; D013329:Structure-Activity Relationship
D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C054598:corticostatin; D006096:Gramicidin; D000001:Calcimycin; D012964:Sodium; D011803:Quinine; D009543:Nifedipine