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

Morphine stimulates prolactin and growth hormone secretion, so the identification of brain peptides with opiate-like activity (methionine-enkephalin and leucine-enkephalin) raised the possibility that these peptides, beside their role as modulators of pain, could also be involved in the control of neuroendocrine functions. The authors did in fact find that Met-enkephalin administered intraventricularly led to a stimulation of prolactin and growth hormone release. 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. 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. The authors 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.