CLONIDINE PREVENTS CORTICOTROPIN RELEASING FACTOR-INDUCED EPILEPTOGENIC ACTIVITY IN RATS

Studies have shown that intracerebroventricular (i.c.v.) injection (10-20-mu-g) of corticotropin releasing factor (CRF) in rats induces epileptiform activity characterized by a regular (pacemaker-like) spiking pattern located in hippocampal leads. CRF has also been shown to increase the firing rate of noradrenergic neurons in the locus ceruleus. Our experiments clarified the possible role of norepinephrine (NE) in mediating hippocampal activity of CRF. Intraperitoneal (i.p.) injection of the alpha-2-agonist clonidine at a dose of 0.5-5-mu-g/kg prevented, in a dose-related manner, the hippocampal epileptiform activity induced by CRF (20-mu-g i.c.v.). Our results suggest a possible role of NE in CRF-induced spiking activity

alpha-1,4-Galactosyltransferase-catalyzed glycosylation of sugar and lipid modified Leu-enkephalins

Glycosylation of therapeutic peptides has been reported to improve delivery and targeting of various vaccines and drugs to specific cells/tissues. However, chemical synthesis of complex oligosaccharide derivatives via conventional methods can be challenging due to the need for several orthogonal hydroxyl group protections. Liposaccharyl galactosyltransferase C, a naturally occurring glycosyltransferase enzyme from Neisseria meningitidis, was found to have the ability to transfer a galactosyl moiety to glyco(lipo)peptides. An enzymatic glycosylation of Leu-enkephalin glyco(lipo)peptides was developed and optimized in this study in order to prepare pain regulating peptides with potentially improved central nervous system delivery