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Centurion D, Ortiz MI, Saxena PR, Villalon CM: The atypical 5-HT2 receptor mediating tachycardia in pithed rats: pharmacological correlation with the 5-HT2A receptor subtype. Br J Pharmacol. 2002 Mar;135(6):1531-9.
1. In pithed rats, 5-HT mediates tachycardia both directly (by 5-HT (2) receptors) and indirectly (by a tyramine-like effect). The receptor mediating tachycardia directly has been classified as an 'atypical' 5-HT (2) receptor since it was 'weakly' blocked by ketanserin. Moreover, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT (2) agonist, failed to mimic 5-HT-induced tachycardia. Since 5-HT (2) receptors consist of 5-HT (2A), 5-HT (2B) and 5-HT (2C) subtypes, this study investigated if these subtypes mediate the above response. 2. In pithed rats, intraperitoneally (i.p.) pre-treated with reserpine (5 mg kg (-1)), intravenous (i.v.) administration of 5-HT, 5-methoxytryptamine (5-MeO-T), 1-(3-chlorophenyl) piperazine (mCPP) and 5-carboxamidotryptamine (5-CT) (10, 30, 100 and 300 microg kg (-1) each), produced dose-dependent tachycardic responses. Interestingly, DOI (10 - 1000 microg kg (-1), i.v.) induced only slight, dose-unrelated, tachycardic responses, whilst the 5-HT (2C) agonist, Ro 60-0175 (10 - 1000 microg kg (-1), i.v.), produced a slight tachycardia only at 300 and 1000 microg kg (-1). In contrast, sumatriptan and 1-(m-trifluoromethylphenyl)- piperazine (TFMPP) were inactive. The rank order of potency was: 5-HT > or =5-MeO-T> mCPP > or =5-CT > or =DOI > Ro 60-0175. 3. The tachycardic responses to 5-HT, which remained unaffected after i.v. saline (0.3 and 1 ml kg (-1)) or propranolol (3 mg kg (-1)), were selectively blocked by the 5-HT (2A) antagonists ketanserin (30 and 100 microg kg (-1)) or spiperone (10 and 30 microg kg (-1)) as well as by the non-selective 5-HT (2) antagonists, ritanserin (10 and 30 microg kg (-1)) or mesulergine (100 microg kg (-1)). Remarkably, these responses were unaffected by the antagonists rauwolscine (5-HT (2B)), SB204741 (5-HT (2B/2C)) or Ro 04-6790 (5-ht (6)) (300 and 1000 microg kg (-1) each). 4. These results suggest that the 'atypical' 5-HT (2) receptors mediating tachycardia in reserpinized pithed rats are pharmacologically similar to the 5-HT (2A) receptor subtype. |
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