Factors involved in the inactivation of vasopressin after intracerebroventricular injection in mice.
Behavioral excitation induced by intracerebroventricularly administered vasopressin in mice is very short-lasting, suggesting a half-life of the injected peptide of only a few minutes. The results of the present study suggest that vasopressin and related peptides are too hydrophilic to penetrate lipid membranes readily by passive diffusion and that passive diffusion from the extracellular space into cells or the bloodstream is an unlikely mechanism of inactivation. Pharmacological desensitization (tachyphylaxis) occurs after higher doses, but does not seem to be the major factor responsible for the short duration of action. Some deaminoanalogs of vasopressin, however, show a prolonged action, suggesting that degradation by (an) aminopeptidase(s) is a major route of inactivation. These results also suggest that vasopressin-degrading aminopeptidases are accessible from the extracellular space.
D000818:Animals; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship; D013618:Tachyphylaxis; D014667:Vasopressins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000633:toxicity
D014667:Vasopressins