Diverse Effects of Norepinephrine on Vasopressin Release may Reflect Modulation by Hypotonicity

Abstract Previous studies in this laboratory and others have demonstrated both stimulation and inhibition of vasopressin release by norepinephrine. In other regions of the central nervous system, diverse effects of norepinephrine reflect activation of different types of adrenergic receptors and the interaction of norepinephrine with other regulatory signals. In this study, the role of these two mechanisms in the diverse action of norepinephrine on vasopressin release were examined using organ-cultured explants of the hypothalamo-neurohypophyseal system. Receptor-specific adrenergic agonists were found to have different effects on vasopressin release, and their effects were dependent upon whether they were delivered in isotonic saline or distilled water. When delivered in isotonic saline at a concentration of 10(-5) M, norepinephrine and phenylephrine, an alpha(1)-adrenergic agonist, increased vasopressin release (P< 0.005 and P< 0.025, respectively); isoproterenol (10(-5) M), a beta-adrenergic agonist, did not alter vasopressin release; and clonidine, an alpha(2)-adrenergic agonist, was ineffective at 10(-5) M, but stimulated vasopressin release at 10(-4) M (P<0.024). However, when these agonists were delivered in 10 mul of distilled water, their effects on vasopressin release were different. This amount of distilled water lowered the osmolality of the culture medium by 3 to 5 mosmol/kg H2O, but did not significantly alter vasopressin release. Vasopressin release was reduced below basal levels when norepinephrine (10(-5) M) or clonidine (10(-6) M) were delivered in distilled water (P<0.025), but it was not significantly different from basal when phenylephrine or isoproterenol (10(-5) M) were delivered in distilled water. These data support the hypothesis that osmotic signals modulate the effect of norepinephrine on vasopressin release, and suggest that, at least in part, this reflects modulation of the type of adrenergic receptor dominating the regulation of vasopressin release.