The activity of peptides of the endothelin family in various mammalian smooth muscle preparations.
The activity of natural endothelins such as ET-1, ET-2, ET-3 and of sarafotoxin S6b (SRFTX) as compared to that of the C-terminal hexapeptide ET-(16-21) was investigated in several smooth muscle preparations in the presence of indomethacin, captopril, bestatin and thiorphan. In some tissues (rat thoracic aorta, guinea-pig ileum, human urinary bladder, renal pelvis or renal artery), ET-(16-21) had little if any agonist activity. In other preparations (guinea-pig bronchus, rat vas deferens, rabbit pulmonary artery) ET-(16-21) was a full agonist. The amidated form of ET-(16-21) was either inactive or less potent than ET-(16-21). These findings provide evidence that at least two receptors exist for peptides of the ET family; these receptors were termed ETA and ETB. ET-(16-21) is a full agonist at ETB receptors while being inactive or weakly active at ETA receptors. The free acid of tryptophan in position 21 plays a key role in the activity of these peptides at ETB receptors.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Giuliani
S
S
Patacchini
R
R
Rovero
P
P
Giachetti
A
A
Meli
A
A
D000818:Animals; D004558:Electric Stimulation; D016232:Endothelins; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D016232:Endothelins; D010446:Peptide Fragments; D010455:Peptides; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D007213:Indomethacin