Cholecystokinin, acting through the A receptor subtype, stimulates the proliferative activity of adrenocortical cells and thymocytes in the rat

Cholecystokinin (CCK) is a multifunctional regulatory peptide, which acts t hrough two main subtypes of receptors, named CCK-A and CCK-B. Evidence indi cates that CCK modulates cell proliferation in various tissues in a paracri ne manner, and proofs are available of the presence of CCK in both adrenal glands and thymus. Hence, we have investigated the possible mitogenic actio n of this peptide on these two tissues, by evaluating the parts per thousan d of metaphase-arrested cells after vincristin injection (mitotic index). T he systemic administration of CCK (three subcutaneous injections of 20 nmol /kg, 28, 16 and 4 h before the sacrifice) increased the mitotic index in bo th the outer adrenal and thymus cortexes of immature (20-day-old) rats and the enucleated adrenal gland of adult (2-month-old) animals at day 5 and 8 of regeneration. The simultaneous administration of equimolar doses of a se lective CCK-A receptor antagonist blocked the effect of CCK, while a CCK-B antagonist was ineffective. These findings indicate that CCK exerts a marke d CCK-A-mediated proliferogenic effect on both adrenal cortex and thymus in the rat, the physiological relevance of which, however, remains to be demo nstrated. In fact, the administration of the CCK-A antagonist alone was ine ffective, thereby casting doubts on the role played by endogenous CCK in th e maintenance and stimulation of adrenal and thymus growth.