Effect of AVP and oxytocin on insulin release: involvement of V1b receptors.
We used a number of receptor antagonists to determine which receptors mediate the effect of arginine vasopressin (AVP) and oxytocin (OT) on insulin release. We found that OT (10(-7) M) and AVP (10(-8) M) increased insulin release from the perfused rat pancreas with similar magnitude. The antagonist with potent V1b receptor-blocking activity, dP[Tyr(Me)2]AVP (10(-7) M), abolished the effect of OT and AVP, whereas the highly selective OT receptor antagonist L-366,948 (10(-6) M) did not change the effect of OT, nor did a V1a receptor antagonist, d(CH2)5[Tyr(Me)2]AVP (10(-7) M), change the effect of AVP. The insulin-releasing potency of OT was estimated as 9-fold less than that of AVP in RINm5F cells. Selected AVP and OT antagonists were used to study their antagonism on AVP- and OT-induced insulin release from RINm5F cells, and the order of potencies of antagonists was estimated as dP[Tyr(Me)2]AVP > d(CH2)5[D-Phe2,Ile4]AVP > SR-49059 > d(CH2)5[Tyr(Me)2]AVP > desGly9d(CH2)5[Tyr(Et)2]VAVP (WK-3-6) approximately L-366,948. These results were consistent with the V1b receptor antagonistic activities of the antagonists. d[D-3-Pal]VP, a V1b receptor agonist, increased insulin release dose dependently (10(-9) to 10(-6) M), and this effect was antagonized by dP[Tyr(Me)2]AVP but not by WK-3-6 (10(-6) M). These results suggested that the stimulatory effect of both OT and AVP on insulin release from beta-cells may be mediated by V1b, but not by V1a or OT receptors.
Lee
B
B
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011, USA.
Yang
C
C
Chen
T H
TH
al-Azawi
N
N
Hsu
W H
WH
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002460:Cell Line; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010121:Oxytocin / Q000494:pharmacology*; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000819:agonists / Q000502:physiology*
D065092:Antidiuretic Hormone Receptor Antagonists; D007328:Insulin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010121:Oxytocin