Document Detail

Effect of amitriptyline on adrenergic receptor number and second messenger function in rat brain.
MedLine Citation:
PMID:  24205756     Owner:  NLM     Status:  In-Process    
Radioligand binding studies were done to investigate the effect of chronic administration of Amitriptyline on alpha1-adrenoceptor (alpha1-AR) receptor mediated response to inositol triphosphate (IP3) in rat brain. Our studies revealed a significant decrease in the densities of alpha1-ARs in cortex and cerebellum of rat brain after chronic administration of Amitriptyline (10 mg kg-1 b.wt.). However, there was no significant change in the affinity of [3H]prazosin to alpha1-ARs. Displacement studies showed that Amitriptyline has higher affinity for alpha1-AR with a Ki value of 182+/-16 nM. Significant change was observed in basal IP3 activity in cortex and cerebellum after Amitriptyline exposure. In cortex and cerebellum of experimental rats the NE (Norepinephrine) stimulated IP3 activity was significantly decreased (1460+/-102 DPM/g tissue; p<0.0001; 1188+/-112 DPM/g tissue; p<0.0001), when compared to NE stimulated IP3 activity (4152+/-286 and 3952+/-245 DPM/g tissue, respectively) in control rats. The decrease in NE stimulated IP3 activity in both regions may be due to the significant downregulation of alpha1-ARs in cortex after Amitriptyline exposure as these sites are positively coupled to IP3. The observed significant decrease in alphal-ARs with concomitant decrease in NE stimulated IP3 activity, after Amitriptyline treatment, suggests that Amitriptyline which has high affinity for these sites, acts by modulating the alpha1-AR receptor mediated response in brain.
D Ramakrishna; M N Subhash
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Pakistan journal of biological sciences: PJBS     Volume:  15     ISSN:  1028-8880     ISO Abbreviation:  Pak. J. Biol. Sci.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2013-11-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101247723     Medline TA:  Pak J Biol Sci     Country:  Pakistan    
Other Details:
Languages:  eng     Pagination:  871-6     Citation Subset:  IM    
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