Inhibition of vasopressin secretion by a met-enkephalin (FK 33-824) in humans

Abstract

Abstract.: To investigate the effect of a met-enkephalin analogue, FK 33-824, on renal handling of water, 8 subjects were given 0.5 mg im of the drug or placebo in a cross-over study. In a second trial under the same testing conditions, a 4 mg dose of naloxone iv was given to 6 subjects immediately preceding 0.5 mg FK 33-824 im. Urine and blood samples were collected at hourly intervals. Urinary vasopressin (AVP) and plasma prolactin (Prl) were assayed, and free water clearance (FWC) was calculated. Following the same protocol, a further 6 subjects received 5 IU of lysine vasopressin im 5 min preceding administration of FK 33-824. FK 33-824 significantly (P < 0.001) increased Prl and FWC and reduced urinary concentrations of AVP (P < 0.01). Naloxone pre-treatment failed to modify significantly the latter two responses, while Prl stimulation was inhibited. Lysine vasopressin pre-treatment abolished the effect of FK 33-824 on FWC while the stimulating action on Prl was preserved. These results indicate that in humans FK 33-824 reduces AVP secretion and that this effect is not mediated by naloxone sensitive opiate receptors.