ISSN:
1432-1912
Keywords:
Receptors
;
Serotonin
;
5-HT-Sensitive adenylate cyclase
;
5-HT High affinity binding
;
5-HT Turnover
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Since metergoline (1-methyl-8-beta-carbobenzyloxy-aminomethyl-10-alpha-ergoline) is a potent 5-HT antagonist in peripheral organs, its possible blocking effects on 5-HT receptors in the rat brain were investigated. In vitro, metergoline inhibited both the specific high affinity binding of 3H-5-HT onto synaptosomal membranes (IC 50=18 nM) and the stimulating effect of 10 μM 5-HT on the adenylate cyclase activity in colliculi homogenates from newborn rats (IC 50=12 μM). In vivo, the administration of metergoline (10 mg/kg i.p., 60 min before death) resulted in a significant decrease in the 3H-5-HT binding capacity of synaptosomal membranes from the forebrain of adult rats. Taken together, these data clearly indicated that metergoline is a potent blocker of some serotoninergic receptors in the rat brain. Surprisingly, the changes in 5-HT turnover occurring in the brainstem and in the forebrain 1 h after metergoline (2–10 mg/kg) treatment were similar to those normally induced by a central 5-HT agonist: both the rate of 5-HT utilisation and that of 5-HT synthesis were significantly decreased. These changes were in contrast to the acceleration of 5-HT turnover induced by the administration of another potent central 5-HT antagonist, methiothepin. These results are discussed in relation to the possible existence of several types of serotoninergic receptors in the rat brain. It is possible that the positive feedback regulation of 5-HT turnover is triggered by the blockade of serotoninergic receptors sensitive to methiothepin, but not to metergoline.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00508301
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