Specific binding sites for vasopressin (AVP) were compared in the kidney and posterior pituitary gland from normal and homozygous Brattleboro rats using autoradiography with [3H]-AVP. The specificity of ligand binding was assessed by displacement with AVP analogues differing in specificity and potency. In the kidney, specific [3H]-AVP binding was found in the medulla, with much less in the cortex, in both normal and Brattleboro rats. Binding of [Η]-AVP was displaced most effectively by dDAVP and least by AVP-OH, in line with their relative antidiuretic potencies. In the pituitary gland, specific AVP binding was much higher in the posterior lobe than in the intermediate or anterior lobes. This posterior lobe AVP binding was greatly reduced in Brattleboro rats, even in animals given exogenous AVP to restore their water balance. It was unlikely that neurophysin binding was responsible since there was no correlation between [3H]-AVP displacement and neurophysin binding in a series of analogues slightly modified at the N or C terminus to affect selectively neurophysin or receptor binding. We suggest that specific AVP receptors may be present in the posterior pituitary gland, possibly on or in the AVP terminals themselves, associated with the normal synthesis, packaging and/or transport of AVP granules to the neural lobe.

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