Potent prolactin and growth hormone releasing activity of more analogues of Met-enkephalin

Abstract

MORPHINE stimulates prolactin and growth hormone secretion^1,2, so the identification of brain peptides with opiate-like activity (methionine-enkephalin and leucine-enkephalin)³ raised the possibility that these peptides, beside their role as modulators of pain⁴, could also be involved in the control of neuro-endocrine functions. We did in fact find that Met-enkephalin administered intraventricularly led to a stimulation of prolactin and growth hormone release^5–7. β-Endorphin (β-LPH_61–91) was, however, found to be 500 to 2,000 times more potent than Met-enkephalin (β-LPH_61–65) in stimulating the release of the pituitary hormones. Since both peptides show similar affinity for the opiate receptor when binding studies are performed at 0 °C in conditions of minimal enzymatic degradation^8,9, the markedly different biological activities of the two peptides after intracerebral injection are likely to be due to a more rapid inactivation of Met-enkephalin. We show here that the two analogues resistant to enzymatic degradation, [D-Ala²]Met-enkephalin and [D-Ala²]Met-enkephalinamide can stimulate prolactin and growth hormone release after intraventricular injection at a level of potency which is 500 to 5,000 times higher than that of the natural Met-enkephalin molecule.