In vivo potentiation of corticotropin releasing factor activity by vasopressin analogues

Abstract

The ability of the neurohypophyseal hormones and related synthetic peptides to potentiate the action of synthetic ovine corticotropin releasing factor (CRF-41) was examined using male rats whose endogenous CRF release was blocked with chlorpromazine, morphine and nembutal. CRF potency was clearly related to the pressor activity of the analogues. However, the threshold dose for eliciting a significant corticosterone response with the neurohypophyseal hormones was greater than with CRF-41. When arginine vasopressin (VAP) was coadministered with CRF-41 at subthreshold doses of both peptides, a significant corticosterone response was observed. When the neurohypophyseal hormone analogues were compared with regard to intrinsic CRF bioactivity, it was observed that an L-basic residue in sequence position 8 is necessary for high intrinsic activity. With one exception, 1-Deamino-(9-D-Ala) arginine vasopressin, the ability to potentiate the effect of CRF-41 was related to the intrinsic CRF potency of the analogues. These results support previous reports of in vitro potentiation of CRF-41 by AVP and point out the complexity of CRF-neurohypophyseal hormone interaction in vivo.