Release of vasoactive intestinal polypeptide into the cerebrospinal fluid of the fourth ventricle of the rat: involvement of cholinergic mechanism.

Vasoactive intestinal polypeptide (VIP) is found abundantly in the cerebrospinal fluid (CSF). In order to clarify its source in the brain and the control mechanism of its release, cerebral ventricles of urethane-anesthetized male rats were locally perfused with the artificial CSF at a constant rate of 120 microliters/min by means of a push-pull cannula and immunoreactive VIP was continuously measured in the effluents obtained at 10 min intervals. The perfusion with veratridine, a depolarizing agent, at a rate of 5 x 10(-4) M/min, caused a significant (P less than 0.01) increase in the effluent VIP levels when the tip of a cannula was placed in the fourth ventricle but not when it was in the third or the lateral ventricle. The release of VIP into the fourth ventricle was also significantly (P less than 0.05) enhanced by the perfusion with acetylcholine (ACh) at a dose of 3.66 x 10(-5) to 1.83 x 10(-4) M/min. A simultaneous perfusion of hexamethonium (1.9 x 10(-4) M/min) blocked ACh-induced VIP release. These results indicate that VIP is released into the CSF from the wall of the fourth ventricle by a mechanism possibly involving nicotine-sensitive cholinergic pathways.