Brain cholecystokinin and β-endorphin systems may antagonistically interact to regulate tissue DNA synthesis in rat pups

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Previously, we have shown that intracisternal (i.c.) administration of β-endorphin suppresses brain and liver DNA synthesis in rat pups. This finding is consistent with the view that endogeneous CNS β-endorphin plays an important role in controlling postnatal growth. Recent evidence suggests that brain CCK 8, the sulfated carboxyterminal octapeptide fragment of cholecystokinin, may function physiologically as an endogenous opioid antagonist. We now report that CCK 8 injected i.c. together with β-endorphin effectively prevented β-endorphin from inhibiting brain and liver DNA synthesis in 10-day-old rats. CCK 8 blocked the liver DNA effect of β-endorphin via actions within the brain, as subcutaneous administration of CCK 8 was ineffective. In contrast to CCK 8, i.c. administration of CCK 8U (the unsulfated form of CCK 8) together with β-endorphin did not prevent β-endorphin from inhibiting liver DNA synthesis, and only slightly reversed the brain DNA effect. The results obtained support a role for endogenous brain CCK 8 in the modulation of tissue DNA responses to CNS β-endorphin and possibly to other endogenous opioids. If so, interference with brain CCK function could disrupt tissue growth. Thus, normal mammalian development may require a close functional interaction between the cholecystokinin and β-endorphin systems in the brain.