Endothelin (16-21): biphasic effect and no desensitization on the guinea-pig isolated ileum.
1. In the guinea-pig ileum the C-terminal hexapeptide of the endothelins, endothelin (16-21), induced a biphasic effect (relaxation followed by contraction) qualitatively similar to that seen in the responses to endothelins 1 and 3. Both components of the response were concentration-dependent in the range studied (2-100 microM). 2. The response induced by endothelin (16-21) was inhibited in low-sodium (80 mM) medium. 3. Repeated administration of endothelin (16-21) induced no desensitization of the preparation, contrasting with the tachyphylaxis induced by endothelin-1 and endothelin-3 in the guinea-pig ileum. 4. Tissues rendered tachyphylatic to endothelin-1 or endothelin-3 responded normally to endothelin (16-21). 5. The results suggest that the C-terminal tail of the endothelins contains the message for the biphasic response, whereas the N-terminal domain may be responsible for the strong binding to the receptor and for the tachyphylactic properties of endothelin-1 and endothelin-3, in the guinea-pig isolated ileum. However, the possibility that endothelin (16-21) may be acting on a site other than the endothelin receptor cannot be ruled out.
Department of Biophysics, Escola Paulista de Medicina, SP, Brazil.
N
N
Miasiro
C R
CR
Nakaie
A C
AC
Paiva
D000595:Amino Acid Sequence; D000818:Animals; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D017466:Receptors, Endothelin / Q000187:drug effects; D012964:Sodium / Q000502:physiology; D013618:Tachyphylaxis / Q000502:physiology
D016232:Endothelins; D010446:Peptide Fragments; D017466:Receptors, Endothelin; C061533:endothelin (16-21); D012964:Sodium