Facilitation of passive avoidance response by newly synthesized cationized arginine vasopressin fragment 4-9 in rats.
The effects of a newly synthesized cationized arginine vasopressin fragment 4-9 analogue (C-AVP-(4-9)) on learning and memory in rats were studied by the passive avoidance test. C-AVP-(4-9) and its parent peptide, arginine vasopressin fragment 4-9 (AVP-(4-9)), a well known potent neuropeptide, were subcutaneously injected 1.5 hr prior to the retention test. The most effective doses of C-AVP-(4-9) and AVP-(4-9) were 8.6 x 10(-2) and 1.3 nmol/kg, respectively. To evaluate the distribution of C-AVP-(4-9) in the control nervous system (CNS), apparent tissue-plasma concentration rations (Kp.app) of intravenously administered radioiodinated C-AVP-(4-9) (125I-C-AVP-(4-9)) in the CNS in mice were determined. At the apparent steady state of plasma concentration of 125I-C-AVP-(4-9), the Kp.app values of the 125I-C-AVP-(4-9) in the cerebrum, cerebellum and spinal cord were over 12 times higher than that of the vascular space marker which slightly penetrates the BBB. Moreover, the rat cerebral homogenate converted C-AVP-(4-9) into its parent peptide AVP-(4-9). These results suggest that the potent effects of C-AVP-(4-9) on learning and memory may be due to AVP-(4-9) generated as a result of distribution and metabolism of peripherally administered C-AVP-(4-9) in the CNS.
Tanabe
S
S
Yakult Central Institute for Microbiological Research, Tokyo, Japan.
Shishido
Y
Y
Furushiro
M
M
Kado
K
K
Hashimoto
S
S
Yokokura
T
T
Ohsawa
T
T
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002412:Cations / Q000378:metabolism / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D007275:Injections, Intravenous; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012153:Retention, Psychology / Q000187:drug effects
D002412:Cations; D010446:Peptide Fragments; D001127:Arginine Vasopressin; C045881:argipressin (4-9)