Sumatriptan contracts large coronary arteries of beagle dogs through 5-HT1-like receptors.
The effects of 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT), methysergide and sumatriptan were studied on endothelium-denuded rings of beagle dog large coronary arteries. Submicromolar concentrations of the compounds contracted the rings with the order of potency 5-CT > 5-HT > sumatriptan = methysergide. Concentrations greater than 2 microM of both 5-HT and 5-CT, and 60 mumol/l methysergide also caused concentration-dependent relaxation. Sumatriptan did not cause relaxation. Peak intrinsic activities relative to the plateau contraction to sumatriptan (1.00), were 5-CT 0.47, 5-HT 0.87 and methysergide 0.51. Ketanserin 1 mumol/l affected neither contractile responses nor relaxant responses to 5-CT, methysergide and sumatriptan and only caused marginal blockade of the contractile effects of 5-HT. Methiothepin 200 nM shifted the concentration-contractile response curves by around 2 log units, as expected from its affinity for 5-HT1-like receptors. The rank order of contractile potency of the agonists, the antagonism by methiothepin and the resistance to blockade by ketanserin are consistent with a nearly exclusive involvement of 5-HT1-like receptors. Isolated large coronary arteries from beagle dogs may be a suitable model for the study of human coronary artery 5-HT1-like receptors that are involved in the spasm observed with 5-HT and sumatriptan.
Parsons
A A
AA
Smith Kline Beecham Pharmaceuticals, Welwyn, Herts, United Kingdom.
Stutchbury
C
C
Raval
P
P
Kaumann
A J
AJ
D000818:Animals; D001158:Arteries / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D018170:Sumatriptan
D007211:Indoles; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D012701:Serotonin; D011189:Potassium Chloride; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D008784:Methysergide