The atypical 5-HT2 receptor mediating tachycardia in pithed rats: pharmacological correlation with the 5-HT2A receptor subtype.

Abstract

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.

• Authors: David Centurión, Mario I Ortiz, Pramod R Saxena, Carlos M Villalón
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 135 Issue 6 Pg. 1531-9 (Mar 2002) ISSN: 0007-1188 [Print] England
• PMID: 11906967 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Free Radical Scavengers
• Receptor, Serotonin, 5-HT2A
• Receptors, Serotonin
• Serotonin Receptor Agonists
• Vasoconstrictor Agents
• Serotonin
• Reserpine
• Norepinephrine

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Blood Pressure (physiology)
• Dose-Response Relationship, Drug
• Free Radical Scavengers (pharmacology)
• Heart Rate (drug effects, physiology)
• Injections, Intravenous
• Male
• Norepinephrine (pharmacology, physiology)
• Rats
• Rats, Wistar
• Receptor, Serotonin, 5-HT2A
• Receptors, Serotonin (physiology)
• Reserpine (pharmacology)
• Serotonin (pharmacology, physiology)
• Serotonin Receptor Agonists (pharmacology)
• Tachycardia (metabolism)
• Vasoconstrictor Agents (pharmacology)