Presence of vasoconstrictor 5HT₁‐like receptors revealed by precontraction of rabbit isolated mesenteric artery

Abstract

1 A series of 5-hydroxytryptamine (5-HT) receptor agonists including 5-HT, 5-carboxamidotryptamine (5-CT) and sumatriptan produced little or no contraction of rabbit isolated mesenteric arteries under resting tone conditions, even at concentrations up to 10-4 M. 2 When the same agonists were retested in mesenteric artery preparations pre-contracted with the thromboxane-mimetic, U46619, each demonstrated concentration-related vasoconstrictor activity. 5-CT and 5-HT were especially potent and effective in this model giving EC50 values of 4.3 x 10-9 M and 1.6 x 10-8 M respectively and maximum effects equivalent to those of KCI 80 mM. In preparations precontracted by U46619 (conditions retained throughout the rest of the study) the order of agonist potency was 5-CT > 5-HT > RU 24969 = sumatriptan > 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) > cisapride. 3 The vasoconstrictor effects of 5-CT were competitively antagonized by methiothepin (pA2 8.20) receptors do not make a significant contribution in this model. 6 Hence, precontraction of rabbit mesenteric arteries reveals potent vasoconstrictor effects of 5-HT and related agonists. Based on the agonist potency order and the antagonist studies performed, the receptor subtype responsible has the characteristics of a 5-HTI-like receptor. This study therefore demonstrates a particularly striking example of vasoconstrictor synergy involving 5-HTI-like receptors.

Coupling of an endogenous 5‐HT1B‐like receptor to increases in intracellular calcium through a pertussis toxin‐sensitive mechanism in CHO‐K1 cells

“…Furthermore, sumatriptan has been shown to cause contraction, via a 5-HTlD-like receptor, in a range of isolated vascular smooth muscle preparations presumably through increases in [Ca2+Ji (Parsons et al, 1992;Choppin & O'Connor, 1995). To our knowledge this is the first paper describing the coupling of an endogenous 5-HTlB receptor to increases in [Ca2+Ji through a PTX-sensitive mechanism.…”

Role of α-Adrenergic Receptors in the Effect of the β-Adrenergic Receptor Ligands, CGP 12177, Bupranolol, and SR 59230A, on the Contraction of Rat Intrapulmonary Artery

“…Different mechanisms may underlie PGF 2␣ -induced potentiation of ␣ 1 -ARmediated response. It has been reported that the vasoconstriction induced by stimulation of some receptors can be enhanced, or even uncovered, by increasing tone through Gq protein-coupled receptor pathway (Choppin and O'Connor, 1995;Movahedi and Purdy, 1997). Several studies have shown that the vasoconstriction induced by ␣-AR stimulation can be potentiated by agonists of other G protein-coupled receptors (Fabi et al, 1998;Bhattacharya and Roberts, 2003).…”

Amplification of sumatriptan-induced contraction in rabbit saphenous vein but not in basilar artery

“…However, much of the information on the vascular effects of sumatriptan has been derived from studies using peripheral vascular serotonin receptors. For example, sumatriptan-induced peripheral vascular contraction has been widely studied in the rabbit saphenous vein (9), femoral artery (4), mesenteric artery (5), and iliac artery (36). Because the cardiovascular liabilities of sumatriptan may be related to its ability to constrict coronary arteries (23), sumatriptan has also been studied in coronary arteries from dogs (21) and humans (1).…”