5-HT1-like receptors mediate 5-hydroxytryptamine-induced contraction of guinea-pig isolated iliac artery.
1. The effects of 5-hydroxytryptamine (5-HT) and of the 5-HT1-like receptor agonists, 5-carboxamidotryptamine (5-CT) and sumatriptan (GR43175) were investigated in isolated ring preparations of guinea-pig common iliac artery. 2. The three agonists induced very weak, if any, contractions of unstimulated preparations, whereas they elicited concentration-dependent contractions in preparations given a moderate tone by a threshold concentration of prostaglandin F2 alpha (PGF2 alpha). 3. Under the latter conditions, Emax values for 5-HT and 5-CT reached about 45% of PGF2 alpha maximal effect, whereas the Emax value of sumatriptan was significantly lower (about 35%). The rank order of potency (mean EC50 value, nM) was 5-CT (6.6) greater than 5-HT (22.9) greater than sumatriptan (155). Pargyline, cocaine or deoxycorticosterone were without significant effect on the contractions induced by 5-HT. 4. The 5-HT3 receptor antagonist, (1 alpha H, 3 alpha,5 alpha H-tropan-3-yl) 1-H-indole-3-carboxylic acid ester (ICS 205-930; 1 microM), had no effect on 5-HT-, 5-CT- and sumatriptan-induced contractions. 5. The 5-HT2 receptor antagonist, ketanserin (1 microM) caused only small rightward shifts (concentration-ratios, about 2) in the concentration-response curves to 5-HT, 5-CT and sumatriptan without significantly depressing the maximum effects. 6. In the presence of ketanserin (1 microM), the non-selective 5-HT receptor antagonist, methiothepin (0.1 microM), shifted the concentration-response curves to 5-HT and 5-CT to the right in a parallel manner and to a similar extent for both agonists (respective mean pKB values, 8.07 and 8.27). The effect of sumatriptan was also antagonized by methiothepin, but solvent effects precluded quantitative analysis of this antagonism. 7. It is concluded that 5-HT1-like receptors mediate the contractions induced by 5-HT, 5-CT and sumatriptan in guinea-pig isolated iliac artery. For reasons not yet understood, these receptors are detected only when the tissues are moderately pre-contracted by PGF2alpha.
Sahin-Erdemli
I
I
Preclinical Research, Sandoz Pharma AG, Basel, Switzerland.
Hoyer
D
D
Stoll
A
A
Seiler
M P
MP
Schoeffter
P
P
D000818:Animals; D006168:Guinea Pigs; D007083:Iliac Artery / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D018170:Sumatriptan; D000077526:Tropisetron; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D007211:Indoles; D011985:Receptors, Serotonin; D013449:Sulfonamides; D012701:Serotonin; D008719:Methiothepin; D000077526:Tropisetron; D018170:Sumatriptan; C047087:5-carboxamidotryptamine; D007650:Ketanserin