Dynorphin-A and vasopressin release in the rat: A structure-activity study

Abstract The effects on vasopressin (VP) release of three dynorphin-A fragments and two antidynorphin antisera were tested in vivo and in vitro. In vivo, the order of potency to inhibit VP release 30 min upon i.c.v. injection was: dynorphin-A-(1–17) > dynorphin-A-(1–13) > dynorphin-A-(1–8).l.c.v. co-administration of 10 nmoles of the specific endopeptidase-inhibitor cFPAAF-pAB and dynorphin-A-(1–8) also suppressed VP secretion. Dynorphin-A-(1–17) antiserum enhanced VP release 20 and 60 min after i.c.v. injection. The antiserum that recognized dynorphin-A-(1–13) elevated VP plasma levels at 60 min post-injection. In vitro, dynorphin-A-(1–8) suppressed electrically evoked VP release from the isolated neuroal lobe. VP release was not affected by dynorphin-A-(1–13), dynorphin-A-(1–17), naloxone, or by the anti-dynorphin antisera. These data indicate that dynorphin-A-(1–17), rather than dynorphin-A-(1–8), plays a role in the centrally located control of neurohypophysial VP release, whereas dynorphin-A-(1–8) is involved in the control located in the posterior pituitary. The synthetic intermediate fragment dynorphin-A-(1–13) appears to affect VP release both centrally and peripherally.