ISSN:
1432-1912
Schlagwort(e):
Postsynaptic 5-HT1 receptors
;
Adenylate cyclase
;
Rat hippocampus
;
5-HT1A, 5-HT1B, 5-HT1C, 5-HT2 receptor subtypes
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Summary 1. Serotonin (5-HT) stimulated adenylate cyclase activity in homogenates of rat hippocampus. This effect was pharmacologically characterised with a series of agonists and antagonists of various structural classes. 2. These compounds where also tested in radioligand binding studies using selective ligands for the various subtypes of 5-HT1 and 5-HT2 receptors. 5-HT1A, 5-HT1B and 5-HT1C recognition sites were labelled with [3H]8-OH-DPAT ([3H]8-hydroxy-2-(di-n-propylamino)-tetralin) in pig cortex membranes, [125I]CYP([125I]iodocyanopindolol) in rat cortex and [3H]mesulergine in pig choroid plexus membranes, respectively. 3. The rank order of potency of 13 agonists stimulating adenylate cyclase activity in homogenates of rat hippocampus was in good agreement with the rank order of affinity of these agonists for the 5-HT1A binding site: N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT)〉5-carboxamidotryptamine (5-CT)〉8-OH-DPAT〉5-HT〉 5-methoxytryptamine (5-OCH3T)〉d-LSD〉5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969)〉α-methylserotonin (α-CH3-5-HT)〉dopamine〉2-methylserotonin (2-CH3-5-HT). The correlation between the respective potencies and affinities of these agonists was r=0.934, P〈0.001. 4. There was no correlation between stimulation of adenylate cyclase activity by these agonists and their affinity for 5-HT1B, 5-HT1C or 5-HT2 binding sites. r=0.381–0.108, P〈0.20–0.73. 5. Potent antagonists at D-1 receptors (SCH 23390), 5-HTM receptors (ICS 205-930), 5-HT2-receptors (ketanserin) and 5-HT1C-receptors (mesulergine) antagonised the 5-HT stimulated adenylate cyclase activity only at very high concentrations. In contrast, spiperone and metitepin were potent antagonists of the effect of 5-CT and 5-HT on adenylate cyclase. The use of these selective antagonists allowed to exclude the possibility that 5-HT stimulates adenylate cyclase activity in rat hippocampus through D-1, 5-HTM, 5-HT2 or 5-HT1C receptors. 6. These data support the concept that 5-HT stimulated adenylate cyclase activity in rat hippocampus is mediated by a 5-HT1A receptor.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00500006
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