Disease relevance of 5HTR2A

• The 5-HT-induced endothelial proliferation was reversed by 5-HT2 receptor antagonists and pertussis toxin [1].
• A specific 5-HT2 antagonist (metrenperone, 0.05 mg/kg of body weight) was administered IM 30 minutes before the cattle were given a 5-minute IV 5-HT infusion [2].

High impact information on 5HTR2A

• These data suggest that the mitogenic effect of 5-HT on endothelial cells is mediated by the 5-HT2 receptor, which is coupled to a G protein [1].
• Ketanserin, a high-affinity ligand for 5-HT2 type receptors, was ineffective in displacing [3H]5-HT binding at concentrations up to 4 microM indicating a 5-HT1 receptor as the primary receptor type isolated [3].
• It has been shown previously that serotonin stimulates the production of prostacyclin by bovine aortic smooth muscle cells in culture, via 5-HT2 receptors (Coughlin SR, Moskowitz MA, Antoniades HN, Levine L. Proc Natl Acad Sci USA 1981;78:7134-7138) [4].
• In addition, both 5-HT2- and 5-HT3-selective agents are essentially inactive at these binding sites [5].
• These responses were effectively blocked by the 5-HT1B receptor antagonist, isamoltane, the 5-HT1B/5-HT2 receptor antagonist, methiothepin, and the eNOS selective antagonists (0.01-10 microM): L-Nomega -monomethyl-L-arginine (L-NMMA) and L-N omega-iminoethyl-L-ornithine (L-NIO) [6].

Biological context of 5HTR2A

• The effect of binding of methysergide to the allosteric site would lead to a conformational change of the 5-HT2-receptor, thereby only allowing the production of a residual 5-HT-induced contraction [7].
• A paradox: the 5-HT2-receptor antagonist ketanserin restores the 5-HT-induced contraction depressed by methysergide in large coronary arteries of calf. Allosteric regulation of 5-HT2-receptors [7].
• This indicates that 5-HT2 receptors but not adrenergic receptors are involved in the vasoconstriction [8].
• Cinanserin alone did not induce desensitization or up-regulation of the 5-HT2 receptor coupled response at 0.1 microM [9].
• Agonist regulation of 5-hydroxytryptamine2 (5-HT2) receptors was studied in calf aortic smooth muscle cultures incubated in a quiescent, defined synthetic medium that does not stimulate cell proliferation, but that provides cells with supplements that maintain cell viability [9].

Anatomical context of 5HTR2A

• Pretreatment with S(-)propranolol or ketanserin also attenuated serotonin-induced contraction, demonstrating that serotonin mediates contraction through both 5-HT1A and 5-HT2 receptors in bovine large coronary arteries [10].
• We conclude that the first phase of the serotonin CRC in rabbit femoral artery was mediated predominantly by 5-HT2 receptors and that the second phase was mediated by alpha 1-adrenoceptors [11].
• Target size analysis of serotonin 5-HT1 and 5-HT2 receptors in bovine brain membranes [12].
• The data indicates the presence of 5-HT2 serotonergic receptors in the bronchial artery of these species [13].
• Two classes of [3H]spiperone binding sites in bovine neurohypophysis: D-2 receptors and putative 5-HT2 receptors [14].

Associations of 5HTR2A with chemical compounds

• Both agents display moderate affinity for histamine (H1), alpha-adrenergic2, and 5-HT2 binding sites [15].
• Contractions induced by 8-hydroxy-2-(di-n-propylamino)-tetralin or alpha-methylserotonin maleate were attenuated by pretreatment with S(-)propranolol (2.6 microM), a relatively selective 5-HT1A and 5-HT1B receptor antagonist, and ketanserin (0.3 microM), a selective 5-HT2 receptor antagonist, respectively [10].
• The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor [16].
• Phenoxybenzamine occludes the 5-HT2-receptor in the R-state but not in the R'-state [17].
• Effects of tryptamine mediated through 2 states of the 5-HT2 receptor in calf coronary artery [18].

References