Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein: effect of selective 5‐HT 1F receptor agonists and PGF 2α

Contractile responses to ergotamine, sumatriptan and the novel 5‐HT 1F receptor agonists, LY334370 and LY344864 were examined using the rabbit saphenous vein. Ergotamine (pEC 50 =8.7±0.06) was 30 fold more potent than 5‐hydroxytryptamine (5‐HT) (pEC 50 =7.2±0.13) and 300 fold more potent than sumatriptan (pEC 50 =6.0±0.08) in contracting the rabbit saphenous vein in vitro . The selective 5‐HT 1F receptor agonists, LY334370 or LY344864 (up to 10 −4   M ), did not contract the rabbit saphenous vein. The contractile response to ergotamine in this tissue resulted from activation of both alpha 1 and 5‐HT 1B/1D receptors based on the observation that prazosin (10 −6   M ), an α‐adrenoceptor antagonist, and GR127935 (10 −8   M ) a 5‐HT 1B/1D receptor antagonist, dextrally shifted the contractile response to ergotamine. In contrast, prazosin (10 −6   M ) did not alter contraction to sumatriptan whereas GR127935 (10 −8   M ) was a potent antagonist (−log K B =10.0) suggesting that sumatriptan‐induced contraction of the rabbit saphenous vein was mediated only by activation of receptors similar or identical to 5‐HT 1B/1D receptors. PGF 2α (3×10 −7   M ) produced a modest increase (approximately 5.0–10.0% maximum PGF 2α contraction) in saphenous vein force. Precontraction with PGF 2α (3×10 −7   M ) dramatically augmented the potency and maximal contractile response to sumatriptan (pEC 50 =7.1) and modestly enhanced the contractile potency of ergotamine (pEC 50 =9.0) in the rabbit saphenous vein. However, PGF 2α (3×10 −7   M ) only unmasked a contraction to the 5‐HT 1F receptor agonists when concentrations exceeded 10 −5   M , concentrations considerably higher than their 5‐HT 1F receptor affinities. LY334370 (10 −6   M ) pretreatment did not alter contraction to either sumatriptan or ergotamine and a higher concentration (10 −5   M ) of LY334370 or LY344864 inhibited contraction to sumatriptan. Thus, activation of 5‐HT 1F receptors will not induce vascular contraction (either alone or following modest tone with PGF 2α ) or augment contraction to other contractile agonists in the rabbit saphenous vein.British Journal of Pharmacology (2000) 131 , 562–568; doi: 10.1038/sj.bjp.0703587