Cyclic GMP formation in rat cerebellar slices is stimulated by endothelins via nitric oxide formation and by sarafotoxins via formation of carbon monoxide.
Involvement of a cyclic GMP pathway in signal transduction stimulated by endothelins (ETs) and sarafotoxins (SRTXs) was explored using rat cerebellar slices. These peptides activated the same receptor binding sites (ET-1 and SRTX-b at the picomolar sites; ET-3 and SRTX-c at the nanomolar sites) to produce cyclic GMP, but their signaling pathways differed. The endothelins (ET-1 and ET-3) were found to signal via nitric oxide formation and to involve pertussis toxin-sensitive G-protein(s). The SRTXs (b and c), while also stimulating cyclic GMP production, did so via a pathway which is not L-arginine-dependent, i.e., carbon monoxide formation, and did not involve pertussis-toxin-sensitive G-protein(s). This is the first demonstration that the signaling pathways of endothelins and sarafotoxins may differ, even though they share the same binding sites.
Shraga-Levine
Z
Z
Laboratory of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Galron
R
R
Sokolovsky
M
M
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002248:Carbon Monoxide / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019335:Nitroarginine; D010455:Peptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017466:Receptors, Endothelin / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010455:Peptides; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D014757:Viper Venoms; C089502:sarafotoxin-c; C057354:sarafotoxins s6; D019335:Nitroarginine; D009569:Nitric Oxide; D002248:Carbon Monoxide; D001120:Arginine; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; C072247:cyclo(Trp-Asp-Pro-Val-Leu)