BACKGROUND: Glycans (sugar moieties) are post-translational modifications on proteins acting as signaling molecules. Sialic acid is such a glycan and the α2,8-linked polysialic acid (PSA) has a restricted distribution within the brain, densely concentrated within the nucleus of the solitary tract (NTS), the primary site of termination of cardiopulmonary afferents. The aim was to determine if altering glycans within the NTS alters tonic or reflex cardiorespiratory function.
METHODS: In vivo electrophysiological recording of blood pressure (BP), heart rate (HR), sympathetic (SNA) and phrenic (PNA) nerve activities in urethane anesthetized rats was conducted before and after microinjections of enzymes that remove glycans from proteins - neuraminidase (NEU) and Peptide-N-Glycosidase F (PNGase-F) - were made into the brain region containing the NTS. The responses to phenylbiguanide, phenylephrine and sodium nitroprusside were determined before and after enzyme injection.
RESULTS: NEU (n=6) evoked large increases in BP, HR and SNA and a reduction in expired CO2. Furthermore, sympathetic baroreceptor and Bezold –Jarisch reflexes were significantly attenuated or eliminated. In contrast, vehicle (n=2) or PNGase-F (n=2) failed to evoke any changes in BP, HR or SNA and very small if any deficits were seen in reflex function.
CONCLUSIONS: NEU and PNGase-F act as enzymes cleaving sugar residues differently. NEU removes sialic acid residues from the termini of all membrane attached sugars. The results suggest that cleavage of PSA in the NTS alters the transmission of vagal afferent information elevating BP, HR and SNA. In contrast PNGase-F, a deglycosylation enzyme acting only on N-linked sugars on glycoproteins, suggests that the sialylation involved in regulating BP, HR and SNA is not on N-linked oligosaccharides in the NTS, but may be carried by O-linked sugars attached to proteins or glycolipids. Immunohistochemical verification of the effect of these enzymes on PSA distribution is underway.
DISCLOSURE: N/A