Hypo-and hyperthyroidism affect the ATP, ADP and AMP hydrolysis in rat hippocampal and cortical slices.
The presence of severe neurological symptoms in thyroid diseases has highlighted the importance of thyroid hormones in the normal functioning of the mature brain. Since, ATP is an important excitatory neurotransmitter and adenosine acts as a neuromodulatory structure inhibiting neurotransmitters release in the central nervous system (CNS), the ectonucleotidase cascade that hydrolyzes ATP to adenosine, is also involved in the control of brain functions. Thus, we investigated the influence of hyper-and hypothyroidism on the ATP, ADP and AMP hydrolysis in hippocampal and cortical slices from adult rats. Hyperthyroidism was induced by daily injections of l-thyroxine (T4) 25 microg/100 g body weight, for 14 days. Hypothyroidism was induced by thyroidectomy and methimazole (0.05%) added to their drinking water for 14 days. Hypothyroid rats were hormonally replaced by daily injections of T4 (5 microg/100 g body weight, i.p.) for 5 days. Hyperthyroidism significantly inhibited the ATP, ADP and AMP hydrolysis in hippocampal slices. In brain cortical slices, hyperthyroidism inhibited the AMP hydrolysis. In contrast, hypothyroidism increased the ATP, ADP and AMP hydrolysis in both hippocampal and cortical slices and these effects were reverted by T4 replacement. Furthermore, hypothyroidism increased the expression of NTPDase1 and 5'-nucleotidase, whereas hyperthyroidism decreased the expression of 5'-nucleotidase in hippocampus of adult rats. These findings demonstrate that thyroid disorders may influence the enzymes involved in the complete degradation of ATP to adenosine and possibly affects the responses mediated by adenine nucleotides in the CNS of adult rats.
Bruno
Alessandra Nejar
AN
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Ramiro Barcellos 2600-ANEXO, 90035-003 Porto Alegre, RS, Brazil.
Diniz
Gabriela Placoná
GP
Ricachenevsky
Felipe Klein
FK
Pochmann
Daniela
D
Bonan
Carla Denise
CD
Barreto-Chaves
Maria Luiza M
ML
Sarkis
João José Freitas
JJ
D015720:5'-Nucleotidase / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D013956:Antithyroid Agents / Q000494:pharmacology; D001081:Apyrase; D002540:Cerebral Cortex / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006868:Hydrolysis; D006980:Hyperthyroidism / Q000139:chemically induced / Q000503:physiopathology*; D007037:Hypothyroidism / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013965:Thyroidectomy; D013974:Thyroxine / Q000494:pharmacology
D000227:Adenine Nucleotides; D015703:Antigens, CD; D013956:Antithyroid Agents; D000249:Adenosine Monophosphate; D008713:Methimazole; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; D000251:Adenosine Triphosphatases; D001081:Apyrase; C067869:CD39 antigen; D013974:Thyroxine