Long-term inhibition of stress-induced adrenocorticotropin release by intracerebral administration of a monoclonal antibody to rat corticotropin-releasing factor together with ricin a chain and monensin.
Abstract Previous studies have shown that microinjection of cytotoxic lgG2a monoclonal antibody to rat/human corticotropin-releasing factor (CRF-MAb) into the hypothalamic paraventricular nucleus of Long Evans rats resulted in antibody uptake into specific neurons of the paraventricular nucleus. We tested the hypothesis that this neuronal uptake may allow non-linked toxins to enter into specific neurons. The effects of central or peripheral administration of a mix containing CRF-MAb and cellular toxins (toxin/ CRF-MAb) on plasma adrenocorticotropin levels were determined before and after exposure to ether stress in freely moving rats. Peripheral injection (jugular vein) of the toxin/CRF-MAb mix or injection into the supraoptic nuclei did not affect resting or stress-induced adrenocorticotropin secretion. In contrast, bilateral injection of the same mix into the paraventricular nucleus or the lateral ventricle caused a consistent 70% reduction of the ether stress-induced adrenocorticotropin release but had no significant effect on the resting adrenocorticotropin levels. The blocking effect of intracerebroventricular administration disappeared after 24 h whereas the blockade persisted for at least 15 days after local injection into the paraventricular nucleus. The injection into the paraventricular nucleus of CRF-MAb without toxins restricted the inhibitory effects to 24 h. These data suggest that administration of a mix of toxins added to a specific lgG2a monoclonal antibody to CRF resulted in a long-term interference with the control of adrenocorticotropin secretion. This new approach may be of use for elucidating the physiological roles of different central peptidergic systems.
Menzaghi
F
F
Laboratory of Cellular Biology, INSERM U 308, 54000 Nancy, France.
Burlet
A
A
Oers
J W
JW
Tilders
F J
FJ
Nicolas
J P
JP
Burlet
C
C