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Braz. j. med. biol. res ; 39(11): 1493-1499, Nov. 2006. graf
Artículo en Inglés | LILACS | ID: lil-437828

RESUMEN

In previous studies, we demonstrated biphasic purinergic effects on prolactin (PRL) secretion stimulated by an adenosine A2 agonist. In the present study, we investigated the role of the activation of adenosine A1 receptors by (R)-N6-(2-phenylisopropyl)adenosine (R-PIA) at the pituitary level in in vitro PRL secretion. Hemipituitaries (one per cuvette in five replicates) from adult male rats were incubated. Administration of R-PIA (0.001, 0.01, 0.1, 1, and 10 æM) induced a reduction of PRL secretion into the medium in a U-shaped dose-response curve. The maximal reduction was obtained with 0.1 æM R-PIA (mean ± SEM, 36.01 ± 5.53 ng/mg tissue weight (t.w.)) treatment compared to control (264.56 ± 15.46 ng/mg t.w.). R-PIA inhibition (0.01 æM = 141.97 ± 15.79 vs control = 244.77 ± 13.79 ng/mg t.w.) of PRL release was blocked by 1 æM cyclopentyltheophylline, a specific A1 receptor antagonist (1 æM = 212.360 ± 26.560 ng/mg t.w.), whereas cyclopentyltheophylline alone (0.01, 0.1, 1 æM) had no effect. R-PIA (0.001, 0.01, 0.1, 1 æM) produced inhibition of PRL secretion stimulated by both phospholipase C (0.5 IU/mL; 977.44 ± 76.17 ng/mg t.w.) and dibutyryl cAMP (1 mM; 415.93 ± 37.66 ng/mg t.w.) with nadir established at the dose of 0.1 æM (225.55 ± 71.42 and 201.9 ± 19.08 ng/mg t.w., respectively). Similarly, R-PIA (0.01 æM) decreased (242.00 ± 24.00 ng/mg t.w.) the PRL secretion stimulated by cholera toxin (0.5 mg/mL; 1050.00 ± 70.00 ng/mg t.w.). In contrast, R-PIA had no effect (468.00 ± 34.00 ng/mg t.w.) on PRL secretion stimulation by pertussis toxin (0.5 mg/mL; 430.00 ± 26.00 ng/mg t.w.). These results suggest that inhibition of PRL secretion after A1 receptor activation by R-PIA is mediated by a Gi protein-dependent mechanism.


Asunto(s)
Animales , Masculino , Ratas , Adenosina/análogos & derivados , Adenosina/farmacología , Adenohipófisis , Prolactina , Receptor de Adenosina A1/metabolismo , Transducción de Señal , Toxina del Cólera/farmacología , CMP Cíclico/farmacología , Relación Dosis-Respuesta a Droga , Toxina del Pertussis/farmacología , Fosfolipasas de Tipo C/farmacología , Adenohipófisis/efectos de los fármacos , Prolactina/efectos de los fármacos , Radioinmunoensayo , Ratas Wistar
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