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Novel high‐affinity 3 H‐serotonin binding sites in rat and bovine brain tissue
Author(s) -
Weisberg Ellen,
Teitler Milt
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430260303
Subject(s) - 5 ht receptor , serotonin , ergotamine , receptor , radioligand , binding site , chemistry , biology , medicine , biochemistry , migraine
Five sites (5HT 1A , 5HT 1B , 5HT 1C , 5HT 1D , and 5HT 1E ) have been detected using 3 H‐5HT radioligand methodology and mammalian brain tissue. We report herein that high‐affinity 3 H‐5HT binding to homogenates of bovine and rat caudate and cortical tissues cannot be interpreted without including at least one additional 5HT receptor. Competition studies were performed in rat frontal cortex tissues, using pharmacological blockade of 5HT 1A , 5HT 1B , and 5HT 1C receptors to facilitate examination of other possible sites. Ergotamine, under these conditions, produced a low‐affinity competition K 1 = 1.2 1μM with a Hill coefficient of 1.0. 5‐carboxyamidotryptamine (5CT), under these conditions, produced a complex competition curve, with an overall K 1 value of 101 nM and a Hill coefficient of 0.55. Computer‐assisted analysis of the 5CT competition curve revealed a high‐affinity site (K 1 = 16nM) and a low‐affinity site (K 1 = 802 nM). Therefore, competition curves produced using ergotamine and 5‐CT indicate that there is a site in rat frontal cortical tissue with high affinity for 5HT, 5CT, and low affinity for ergotamine as well as a site with high affinity for 5HT and low affinity for 5CT and ergotamine. The site with high affinity for 5HT, and low affinity for 5CT and ergotamine resembles the 5HT 1E receptor, insofar as these three drugs are concerned. There is no reported site with high affinity for 5HT and 5CT and low affinity for ergotamine (heretofore referred to as 5HT 1F ). The lack of a high‐affinity ergotamine competition for 3 H‐5HT binding to non‐5HT 1A , 5HT 1B , and 5HT 1C sites indicates that there is no detectable 5HT 1D binding in this tissue. In rat striatal tissue both 5CT and ergotamine produced complex competition curves with Hill coefficients less than unity (0.6 and 0.65, respectively). Computer‐assisted analysis indicated that a minority of sites (approximately 35%) displayed high affinity for both ergotamine and 5CT, while 65% of the sites displayed low affinity for both 5CT and ergotamine. The site labeled with 3 H‐5HT displaying high affinity for 5CT and ergotamine coincides with the pharmacological profile of a 5HT 1D site. The site labeled with 3 H‐5HT displaying low affinity for 5CT and ergotamine coincides with the pharmacological profile of the 5HT 1E site. Results from bovine cortical and striatal tissues reinforce the conclusions drawn from the rat brain data. In summary, detailed studies of specific 3 H‐5HT binding to non 5HT 1A‐1C sites indicate that (1) there are detectable 5HT 1D sites in rat striatal tissue but not in rat cortical tissue, (2) there are detectable 5HT 1E sites in rat brain tissue, and (c) a novel high‐affinity 3 H‐5HT binding site possessing high affinity for 5CT and low affinity for ergotamine has been detected in rat and bovine brain tissues. © 1992 Wiley‐Liss, Inc.