Abstract
MORPHINE stimulates prolactin and growth hormone secretion1,2, 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 release5–7. β-Endorphin (β-LPH61–91) was, however, found to be 500 to 2,000 times more potent than Met-enkephalin (β-LPH61–65) 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 degradation8,9, 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.
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