GR-127935-sensitive mechanism mediating hypotension in anesthetized rats: Are 5-HT_5B receptors involved?

The 5-HT_1B/1D receptor antagonist, GR-127935, inhibits hypotensive responses produced by the 5-HT_1A, 5-HT_1B/1D and 5-HT₇ receptor agonist, and 5-HT_5A/5B receptor ligand, 5-carboxamidotryptamine (5-CT), in rats. This work further characterized the above mechanism using more selective 5-HT_1B and 5-HT_1Dreceptor antagonists. Also, expression of 5-HT_5A and 5-HT_5B receptor mRNAs in blood vessels was searched by reverse transcription polymerase chain reaction. Decreases in diastolic blood pressure induced by 5-CT (0.001-10 μg/kg, intravenously) were analyzed in anesthetized rats that had received intravenous vehicle (1 mL/kg), SB-224289 (5-HT_1B antagonist; 0.3 and 1.0 mg/kg), BRL15572 (5-HT_1D antagonist; 0.3 and 1.0 mg/kg), SB-224289 + BRL15572 (0.3 mg/kg, each), or SB-224289 + BRL15572 (0.3 mg/kg, each) + GR-127935 (1 mg/kg). Because only the latter treatment inhibited 5-CT-induced hypotension, suggestive of a mechanism unrelated to 5-HT_1B/1D receptors, the effects of antagonists/ligands at 5-HT_5A (SB-699551, 1 mg/kg), 5-HT₆(SB-399885, 1 mg/kg), and 5-HT_{1B/1D/5A/5B/7} receptors (ergotamine, 0.1 mg/kg) on 5-CT-induced hypotension were tested. Interestingly, only ergotamine blocked 5-CT-induced responses; this effect closely paralleled that of SB-224289 + BRL-15572 + GR-127935. Neither did ergotamine nor GR-127935 inhibit hypotensive responses induced by the 5-HT₇ receptor agonist, LP-44. Faint but clear bands corresponding to 5-HT_5A and 5-HT_5B receptor mRNAs in aorta and mesenteric arteries were detected. Results suggest that the GR-127935-sensitive mechanism mediating hypotension in rats is unrelated to 5-HT_1B, 5-HT_1D, 5-HT_5A, 5-HT₆, and 5-HT₇ receptors. This mechanism, however, resembles putative 5-HT_5B receptors.