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      Influence of Dopaminergic Agonists and Antagonists on Serum Prolactin Concentrations in the Rat



      S. Karger AG

      Dopaminergic antagonists, Dopaminergic agonists, Mechanism of action, Prolactin secretion

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          Inhibitors of dopaminergic neurotransmission, such as reserpine (RES), given alone or combined with α-methyl-p-tyrosine ( α-MpT) or Ro 4-4602, as well as haloperidol (HAL) and sulpiride (SUL), induced highly elevated serum prolactin (Prl) concentrations in intact rats. In contrast, the dopaminergic agonists apomorphine (APO), lisuride hydrogen maleate (LHM), D-amphetamine (AMPH), piribedil and L-dopa greatly lowered the high serum Prl concentrations in female rats induced by i.p. pretreatment with 2 mg/kg RES. Additional inhibition of catecholamine synthesis in RES-treated animals by α-MpT abolished the effect of AMPH, which indicates that the effect of this compound is mediated through newly synthesized dopamine (DA), while the effect of APO and LHM remained unchanged. Inhibition of dopa decarboxylation by Ro 4–4602 within the whole body abolished the effect of L-dopa, while lower dosages of Ro 4–4602, which do not penetrate the blood-brain barrier, had less effect. The noradrenergic receptor-stimulating agent clonidine (CLON) had no Prl-lowering effect in RES-treated female rats. In hypophysectomized rats bearing 4 pituitaries transplanted under the kidney capsule, APO and LSM still lowered serum Prl concentrations, while AMPH had no effect; SUL produced a strong increase. These results support the hypothesis that DA has a dominant role as an inhibitor of Prl secretion by acting itself as the Prl inhibiting factor (PIF) on dopaminergic receptors located within the pituitary.

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          Author and article information

          S. Karger AG
          25 March 2008
          : 22
          : 3
          : 273-286
          Research Laboratories of Schering, AG, Division of Clinical Research and Department of Endocrine Pharmacology, Berlin/Bergkamen
          122634 Neuroendocrinology 1976;22:273–286
          © 1976 S. Karger AG, Basel

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          Page count
          Pages: 14


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