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Table 2 Extensively used serotonin 5HT2A receptor modulators in preclinical studies to evaluate the possible role of serotonin 5HT2A receptors in physiology and pathophysiology of CKDs

From: Understanding Serotonin 5-HT2A Receptors-regulated cellular and molecular Mechanisms of Chronic Kidney Diseases

S. noMechanismsTreatmentsAnimals usedReferences
1Autoregulation1. (i) Serotonin intrarenal bolus injections (0.3, 0.5, 1.0, and 2.0 μg).
(ii) Ketanserin 2 mg/kg/h infusion i.v (high dose); Ketanserin 0.05 mg/kg, followed by 0.1 mg/kg/h i.v infusion (low dose)
Male Wistar ratsLameire et al. [11]
 2. (i) 10-8 mol/L of 5-HT was added to the tissue bath.
(ii) 10-6 mol/L of the 5-HT2 receptor antagonist Ritanserin were locally applied.
(ii) 10-6 mol/L Ritanserin was given first, and after 60 min, 10-8 mol/L 5-HT was added to the tissue bath.
Female Wistar ratsEndlich et al. [12]
3. Serotonin (0.3, 0.5, 0.75, and 1 μg) was injected before and during Ketanserin administration (bolus of 0.05 mg/kg, followed by a sustained infusion of 0. 1 mg/kg/h, dissolved in isotonic saline at a rate of 0.0425 mL/min.Male Wistar ratsVerbeke et al. [13]
 4. (i) Ritanserin 0.6 mg/kg bolus/i.v, followed by an infusion of 1.2 mg/kg/h in isotonic saline, infused at a rate of 0.0425 ml/min.
(ii) Selective 5-HT2 agonist, 2,5-dimethoxy- 4-iodo amphetamine HCl (DOI) intrarenal bolus injections (10, 30, 100, and 300 ng).
(iii) Serotonin intrarenal bolus injections (0.1, 0.3, 0.5, and 0.7 μg) doses without systemic effects*
Male Wistar ratsVerbeke et al. [14]
 5. (i) α-methyl-5HT was administered locally at doses of 0.00000125, 0.000125, 0.00125, 0.0125, 0.025, 0.05, and 0.1 μg/kg (i.a.) via the distal cannula by bolus injection of a maximum vol of 10 μL using a microsyringe, with a gap of 5 min b/w administration of each drug dose.
(ii) Ritanserin (1 mg/kg) (i.v.)
(iii) Spiperone (0.125 mg/kg) (i.v.)
Male Wistar ratsMoran et al. 2008
2Nitric oxide (NO) pathway1. (i) 5HT was administered locally at doses of 0.0125, 0.025, 0.05, and 0.1 mg/kg (i.a.) via the distal cannula by bolus injection of a maximum vol of 10 μL using a microsyringe, with a gap of 5 min b/w administration of each drug dose.
(ii) Ritanserin 1 mg/kg/i.v was administered 10–15 min before i.a. administration of 5-HT.
(iii) Locally administered 5-HT 0.1–50 mg/kg.
Male Wistar ratsMoran et al. 1997
 2. (i) α-methyl-5HT was administered locally at doses of 0.00000125, 0.000125, 0.00125, 0.0125, 0.025, 0.05, and 0.1 μg/kg (i.a.) via the distal cannula by bolus injection of a maximum vol of 10 μL using a microsyringe, with a gap of 5 min b/w administration of each drug dose.
(ii) Ritanserin (1 mg/kg) (i.v.)
(iii) Spiperone (0.125 mg/kg) (i.v.)
Male Wistar ratsMoran et al. [8]
 3. (i) DOI was infused into the renal artery at a rate of 5 mg/kg/min for 30 min, then a recovery period was allowed for 30 min after cessation of the infusion.
(ii) Sarpogrelate infusion into the renal artery at a rate of 100 mg/kg/min for 30 min
Adult mongrel dogs of both sexesTian et al. 2002
3Mitochondrial biogenesis1. (i) 1, 10, and 100 nM of agonist NBOH-2C-CN [4-[2-[[(2-hydroxyl-phenyl) methyl]amino]ethyl]-2,5-dimethoxybenzonitrile dose used to treat isolated renal proximal tubular cells (RPTCs).
(ii) RPTCs were pretreated with 1, 10, and 100 nM Eplivanserin for 24 h.
Isolated RPTCs of female New Zealand white rabbitsHarmon et al. [5]
 2. . RPTC and NRK52-E cells were treated with 10-1 M DOI or vehicle for 24 hIsolated RPTCs of female New Zealand white rabbitsRasbach et al. 2009
4Oxidative stress1. Serotonin (60 mg/kg/i.p)Sprague-Dawley ratsAli et al. [15]
2. Sarpogrelate (30 mg/kg P.O.) for 8 weeksMale Wistar ratsKobayashi et al. [16]
5Inflammation1. Sarpogrelate HCl (30 mg/kg/day) via oral gavage for 12 weeksMale db/m and db/db mice in a C57BLKs/J backgroundLee et al. [17]
2. Whole blood from each of 26 subjects was cultured with 5-HT (150 ng/ml, 1.5 Ag/ml and 15 Ag/ml), and ritanserin (50 ng/ml and 5 Ag/ml)26 healthy volunteers, divided into three subgroups, i.e., 12 younger volunteers, 7 treatment-resistant depressed patients, 7 age- and sex-matched healthy controlsKubera et al. [18]
3. (i) Sarpogrelate solution concentration was adjusted to give mice 3, 30, and 300 mg/kg daily based on the amount of drinking water consumed.
 (ii) 10-1 M of 5-HT and 10-1 M sarpogrelate for 3 h.
Male wild-type C57BL/6 mice
stable C57BL/6 mice proximal tubular epithelial cell line mProx
Hamasaki et al. [19]
4. DOI (0.3 mg/kg/i.p); (0.01; 0.1, 0.3 μg/kg/i.p)Young adult male C57BL/6J miceFelix et al. 2013
6JAK/STAT pathway1. (i) Ketanserin (10 nM)VSMCs of male Sprague-Dawley ratsBanes et al. 2004
 (ii) Ketanserin (5 mg/kg/day)male Sprague-Dawley ratsBanes et al. 2004
7Collagen type IV1. 10-6 mg/L of 5-HT with different conc of serotonin, ketanserin, and sarpogrelate HClIsolated mesangial cells from human glomeruliKasho et al. [20]
8ERK phosphorylation1. 0, 1, and 10 μM of 5-HTMesangial cells of Sprague-Dawley rats
Isolated mesangial cell from glomeruli of male Sprague-Dawley rat
Gooz et al. 2005
Grewal et al. [21]