Dynorphin-A and vasopressin release in the rat: a structure-activity study.
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 neural 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.
Van de Heijning
B J
BJ
Rudolf Magnus Institute, Department of Pharmacology, Utrecht, The Netherlands.
Maigret
C
C
Koekkoek-van den Herik
I
I
Smelik
W F
WF
van Wimersma Greidanus
T B
TB
D000704:Analysis of Variance; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D007106:Immune Sera; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013997:Time Factors
D007106:Immune Sera; D010446:Peptide Fragments; D001127:Arginine Vasopressin; D009270:Naloxone; C026843:dynorphin (1-13); D004399:Dynorphins; C026770:dynorphin (1-8)