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
S. no | Mechanisms | Treatments | Animals used | References |
|---|---|---|---|---|
1 | Autoregulation | 1. (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 rats | Lameire 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 rats | Endlich 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 rats | Verbeke 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 rats | Verbeke 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 rats | Moran et al. 2008 | ||
2 | Nitric oxide (NO) pathway | 1. (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 rats | Moran 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 rats | Moran 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 sexes | Tian et al. 2002 | ||
3 | Mitochondrial biogenesis | 1. (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 rabbits | Harmon et al. [5] |
 2. . RPTC and NRK52-E cells were treated with 10-1 M DOI or vehicle for 24 h | Isolated RPTCs of female New Zealand white rabbits | Rasbach et al. 2009 | ||
4 | Oxidative stress | 1. Serotonin (60 mg/kg/i.p) | Sprague-Dawley rats | Ali et al. [15] |
2. Sarpogrelate (30 mg/kg P.O.) for 8 weeks | Male Wistar rats | Kobayashi et al. [16] | ||
5 | Inflammation | 1. Sarpogrelate HCl (30 mg/kg/day) via oral gavage for 12 weeks | Male db/m and db/db mice in a C57BLKs/J background | Lee 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 controls | Kubera 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 mice | Felix et al. 2013 | ||
6 | JAK/STAT pathway | 1. (i) Ketanserin (10 nM) | VSMCs of male Sprague-Dawley rats | Banes et al. 2004 |
 (ii) Ketanserin (5 mg/kg/day) | male Sprague-Dawley rats | Banes et al. 2004 | ||
7 | Collagen type IV | 1. 10-6 mg/L of 5-HT with different conc of serotonin, ketanserin, and sarpogrelate HCl | Isolated mesangial cells from human glomeruli | Kasho et al. [20] |
8 | ERK phosphorylation | 1. 0, 1, and 10 μM of 5-HT | Mesangial cells of Sprague-Dawley rats Isolated mesangial cell from glomeruli of male Sprague-Dawley rat | Gooz et al. 2005 Grewal et al. [21] |