Effects of sulpiride and apomorphine on prolactin release in adrenalectomized animals. Role of sodium ions

Abstract

The present experiments were performed to demonstrate in vivo the existence of a modulatory role of Na + in the inhibitory control of prolactin (PRL) secretion. Groups of adult male rats were either adrenalectomized (adrenex) or sham-operated (normals) and implanted in the right atrium with a chronic cannula for the infusion of solutions or the sequential withdrawal of blood samples. Four days later, adrenex rats were infused for 1 h with either saline 0.9% or dextrose 5.6% (310 mOsm/kg H 2O) at the rate of 10 ml/kg/h from Time −60 min until Time 0 min. All animals were injected at Time −45 min with sulpiride 0.05 mg/kg. At Time 0 min, some animals received apomorphine 5 mg/kg while others received a 0.05 mg/kg dose of the drug. Blood samples were obtained at −45, −30, −15, 0, 5, 10, 20 and 30 min for PRL assay. Plasma Na + concentration was measured at −45, 0 and 30 min and plasma osmolarity at 0 min in adrenex rats. In normal controls plasma Na + values were measured at the end of the experiment. Binding values ( K D and B max) of pituitary D 2-receptors were measured in adrenex and sham-operated rats using [ 3H]spiroperidol as ligand and d-butaclamol to define non-specific binding. Plasma Na + values remained constant in saline-infused adrenex rats and similar to those of normal controls, while in dextrose-infused adrenex rats they fell progressively during the experimental period and were always lower than in the two other groups. Plasma osmolarity was similar in the two adrenex groups. Sulpiride induced a much greater rise of plasma PRL values in iso-than in hyponatremic adrenex or normal animals. Apomorphine 5 mg/kg exerted a biphasic action on PRL release in adrenex rats, stimulatory first and then inhibitory, but only an inhibitory effect in normal animals. While the inhibitory action of this dose of the drug was similar in all animals, the stimulatory effect was greater in iso- than in hyponatremic adrenex rats. A 0.05 mg/kg dose of apomorphine had only a stimulatory effect in adrenex rats, which was greater in the isonatremic group, but was completely ineffective in normal rats. Binding studies showed the presence of D 2-receptors with a greater binding affinity in the anterior pituitaries of adrenex than in those of normal rats. These results indicate that adrenalectomy enhances the PRL-releasing effect of sulpiride, a dopamine antagonist, probably by sensitizing the postsynaptic D 2 receptor and that hyponatremia may antagonize such an enhancing effect. In conclusion, both the adrenal gland and Na + may intervene in the modulation of the inhibitory control pituitary PRL release.