Effects of peptides in the hypothalamic vasopressinergic nuclei.

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1) Muscarinic agonist, oxotremorine microinjected into the hypothalamic vasopressinergic nucleus (the supraoptic nucleus or the paravetricular nuleus) induced potent antidiuretic effects which were associated with increases in the level of plasma vasopressin. The antidiuretic effects were completely blocked by premicroinjection of muscarinic antagonist, atropine or by preteartment with intravenous injection of vasopressin (V1+V2) receptor antagonist, d (CH2) 5-D-Tyr (Et) -VAVP.2) Neuropeptide, substance P also caused potent antidiuretic effects, when microinjected into the supraoptic nucleus. At the maximal effects of substance P, vasopressin concentration in the urine increased up to approximately 26-fold the control value. Premicroinjection of substance P receptor antagonist, spantide inhibited the antidiuretic effects of substance P. Substance P microinjected into the paraventricular nucleus also demonstrated potent antidiuretic effects.3) A kappa-type opioid peptide, dynorphin (1-13) which colocalizes with vasopressin induced potent antidiuretic effects which accompanied in-creases in the plasma level of vasopressin, when injected into the supraoptic nucleus or the paraventricular nucleus. The effects of the supraoptic injection were inhibited by premicroinjection of naloxone, but were not the effects of the paraventricular injection. Dynophin (2-13) which does not bind to opioid receptors induced approximately equipotent effects to dynorphin (1-13) when injected in the supraoptic nucleus, and it induced much less potent effects than dynorphin (1-13), when injected into the paravetricular nucleus.The results indicate that the stimulation of muscarinic or substance P -receptors in the nuclei by specific agonists induced the release of vasopressin, and that dynorphin (1-13) stimulated the neurons in the paraventricular nucleus through opioid receptors and it stimulated neurons in the supraoptic nucleus via non-opioid receptors, to release vasopressin.