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- Title
The atypical 5-HT[sub 2] receptor mediating tachycardia in pithed rats: pharmacological correlation with the 5-HT[sub2A] receptor subtype.
- Authors
Centuriòn, David; Ortiz, Mario I.; Saxena, Pramod R.; Villalòn, Carlos M.
- Abstract
1 In pithed rats. 5-HT mediates tachycardia both directly (by 5-HT[sub2] receptors) and indirectly (by a tyramine-like effect). The receptor mediating tachycardia directly has been classified as an 'atypical' 5-HT[sub2] receptor since it was'weakly' blocked by ketanserin. Moreover, l-(2.5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). a 5-HT[sub2] agonist, failed to mimic 5-HT-induced tachycardia. Since 5-HT[sub2] receptors consist of 5-HT[sub2A], 5-HT[sub2B]and 5-HT[sub2C] 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[&sup-1;]), intravenous (i.v.) administration of 5-HT, 5-methoxytryptamine (5-MeO-T). l-(3-chlorophenyl) piperazine (mCPP) and 5-carboxamidotryptamine (5-CT) (10, 30,100 and 300 μg kg[&sup-1;] each), produced dose-dependent tachycardic responses. Interestingly, DOI (10-1000 μg kg[&sup-1;], i.v.) induced only slight.dose-unrelaled, tachycardic responses, whilst the 5-HT[sub2C] agonist, Ro 60-0175 (10-1000 μg kg[&sup-1;], i.v.). produced a slight tachycardia only at 300 and 1000μg kg[&sup-1;]. In contrast, sumatriptan and I-(m-trifluoromethylphenyl)- piperazine (TFMPP) were inactive. The rank order of potency was: 5-HT ≥5-MeO-T> mCPP≥ 5-CT≥ DOI>Ro 60-0175. 3 The tachycardic responses to 5-HT, which remained unaffected after i.v. saline (0.3 and 1 ml kg[&sup-1;]) or propranolol (3 mg kg[&sup-1;]), were selectively blocked by the 5-HT[sub2A] antagonists ketanserin (30 and 100 μg kg[&sup-1;]) or spiperone (10 and 30 μg kg[&sup-1;]) as well as by the non-selective 5-HT[sub1] antagonists, ritanserin (10 and 30 μg kg[&sup-1;]) or mesulergine (100 μg kg[&sup-1;]). Remarkably, these responses were unaffected by the antagonists rauwolscine l5-HT[sub2B]), SB204741 (5-HT[sub2B/2C]) or Ro 04-6790 (5-ht[sub6]) (300 and 1000μg kg[&sup-1;]each). 4 These results suggest that the 'atypical' 5-HT[sub2]receptors mediating tachycardia in reserpinized pithed rats are pharmacologically similar to the 5-HT[sub2A] receptor subtype.
- Subjects
TACHYCARDIA; SEROTONIN; ANTIHYPERTENSIVE agents; KETANSERIN; LABORATORY rats
- Publication
British Journal of Pharmacology, 2002, Vol 135, Issue 6, p1531
- ISSN
0007-1188
- Publication type
Article