Differential kinetics of hypocretins in the cerebrospinal fluid after intracerebroventricular administration in rats.
Different potencies for hypocretin-1 and -2 in sleep-wake regulation and feeding after intracerebroventricular (ICV) administration have been reported. These differences were often explained by the selectivity of the two hypocretins for hypocretin receptor-1 and -2, but little attention has been paid to kinetics of hypocretin peptides. We investigated the kinetics of the ICV hypocretin-1 and -2 in rats. ICV hypocretin-1 (10 nmol) increased hypocretin-1 peptide level in the CSF by 800-fold from baseline with the elevation lasting over 4 h. In contrast, after ICV hypocretin-2 (10 nmol), no significant rise in the CSF was found. CSF hypocretin levels were significantly correlated with the biological activities of CSF hypocretin-1 and -2 using the Ca(2+) mobilization assay. Difference in the kinetics of hypocretins should be considered for interpreting ICV effects of hypocretins.
Yoshida
Yasushi
Y
Center for Narcolepsy, Stanford University, 701B Welch Road, 1st Floor, Palo Alto, CA, 94304-5742, USA.
Fujiki
Nobuhiro
N
Maki
Richard A
RA
Schwarz
David
D
Nishino
Seiji
S
D000818:Animals; D002352:Carrier Proteins / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D002460:Cell Line; D006801:Humans; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D018377:Neurotransmitter Agents / Q000134:cerebrospinal fluid*; D000068797:Orexins; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
D002352:Carrier Proteins; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins