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Intracerebroventricular Passive Immunization. II. Intracerebroventricular Infusion of Neuropeptide Antisera Can Inhibit Neuropeptide Signaling in Peripheral Tissues¹

The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, California 92037

Address all correspondence and requests for reprints to: Dr. Catherine L. Rivier, The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037. E-mail: crivier{at}salk.edu

The findings of the preceding article suggest that intracerebroventricular (icv) administration of small amounts (5 µl) of antisera to rats may produce effectual immunoneutralization of peptides in blood/tissues outside of the central nervous system (CNS). In the present work we sought to test this hypothesis by determining the titers of corresponding antibodies in jugular venous plasma after icv infusion of three different antisera: a sheep anti-CRF, a rabbit anti-CRF, and a rabbit anti-GnRH. For all antisera tested, corresponding antibodies were detected in systemic plasma within 30 min of icv infusion of 5 µl antiserum. By 8 h, blood levels of the corresponding antibodies were similar whether the antisera had been infused icv or iv. When the dilutions of antibodies equivalent to those in systemic blood 1–24 h after icv infusion of 5 µl antiserum were employed in rat anterior pituitary cell culture assays, they proved effective at inhibiting CRF- or GnRH-induced hormone secretion. Furthermore, in rats pretreated icv with 5 µl anti-CRF (at -4 h), pituitary ACTH secretion induced by iv CRF (0.3 nmol/kg) was reduced by 88%. Collectively, these data demonstrate that shortly after icv infusion of neuropeptide antisera, the levels of corresponding antibodies found in systemic blood are sufficient to inhibit neuropeptide signaling within peripheral tissues. As icv passive immunization procedures have been used extensively in the investigation of the biological roles of neuropeptides within the CNS, these findings indicate a critical reevaluation of the peripheral vs. CNS functions of neuropeptides.

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