Involvement of 5-HT2A receptors in the elevation of rat serum corticosterone concentrations by quipazine and MK-212.
The possible involvement of 5-HT2A or 5-HT2C receptors in the elevation of serum corticosterone in rats by quipazine (2-(1-piperazinyl)quinoline maleate) and MK-212 (6-chloro-(1-piperazinyl)pyrazine), direct-acting 5-HT receptor agonists, was investigated by the use of two newly available receptor antagonists, SB 200646A (N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea) and MDL 100,907 (R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]- 4-piperidinemethanol). MDL 100,907 blocked the increase in serum corticosterone elicited by quipazine and MK-212 with ED50 values of 0.0028 and 0.0027 mg/kg, s.c., respectively. In contrast, SB 200646A only partially antagonized the serum corticosterone concentration increases by quipazine and MK-212 even at the highest dose tested, 40 mg/kg, i.p. Because published data show the affinities of MDL 100,907 and SB 200646A for 5-HT2C receptors to be nearly identical, whereas the affinity of MDL 100,907 for 5-HT2A receptors is 17500-fold higher than that of SB 200646A, our findings suggest that 5-HT2A receptors rather than 5-HT2C receptors mediate the serum corticosterone increases by both quipazine and MK-212.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
S K
SK
Hemrick-Luecke
R W
RW
Fuller
D000818:Animals; D003345:Corticosterone / Q000097:blood*; D005464:Fluorobenzenes / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011719:Pyrazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011814:Quipazine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D005464:Fluorobenzenes; D007211:Indoles; D010880:Piperidines; D011719:Pyrazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C080864:N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea; D011814:Quipazine; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D014508:Urea; C079049:volinanserin; D003345:Corticosterone