Interaction of beta-casomorphins with multiple opioid receptors: in vitro and in vivo studies in the newborn rat brain

beta-Casomorphins (beta-CMs) are peptidic fragments of bovine beta-casein with potent opioid activity. In view of a possible physiological meaning of these milk-derived compounds, we have studied the affinity of some natural beta-CMs and some semisynthetic analogues for mu-, delta- and kappa-brain opioid receptors in newborn and adult rat. Moreover we have investigated whether a chronic treatment with the potent analogue D-Ala2-beta-CM-4-NH2 during the suckling period could affect mu and delta opioid receptor function. Our findings demonstrate that beta-CMs are mu-oriented compounds both in adult and in newborn rat brain. They display the same mu-affinity in newborn as well as in adult animals, however delta and kappa-affinities appear different, probably due to the lower degree of maturation of these two receptors in the first days of life. A prolonged treatment with D-Ala2-beta-CM-4-NH2 during the preweanling period is able to induce a delay in the ontogenetic increase of delta-receptor affinity, whereas it affects neither the affinity nor the density of mu-receptors. This effect could be related to a general action of opioids on cerebral maturative processes; moreover we point out that a beta-CMs analogue, given orally to newborn animals, can induce modifications at central level, suggesting thus the hypothesis that beta-CMs could be a biologically active peptide in the first stages of life.