Effects of Changes in Hydromineral Balance on Rat Brain Aspartyl, Arginyl, and Alanyl Aminopeptidase Activities

Abstract

In order to examine the possible relationship between the processing and inactivation roles of aminopeptidases and the disruption of water-electrolyte balance, we measured the activities of aspartyl aminopeptidase (Asp-Ap), arginyl aminopeptidase (Arg-Ap) and alanyl aminopeptidase (Ala-Ap) in certain brain areas (hypothalamus, hippocampus, thalamus and brain cortices) and in the pituitary gland in several models of hydrosaline change. The activity of hypothalamic membrane-bound Asp-Ap significantly decreased (more than 50 %) following treatments which induced a hypovolemic state. Aminopeptidase M activity (membrane-bound Ala-Ap activity with low sensitivity to puromycin) was also significantly decreased by 53 % in the thalamus of rats under conditions of hypovolemia plus hyperosmolality in comparison to the control group. These results indicate that aminopeptidases in the central nervous system may be involved in the physiological regulation of hydromineral balance.

Key words

Peptidase - Neuropeptide Degradation - Osmolality - Water-Electrolyte Homeostasis

References

• 1 Bauer K. Role of proteolytic enzymes in neuropeptide metabolism.  INSERM. 1982;  110 475-494
• 2 Graf L, Hui K S, Neidle A, Lajtha A. Neuropeptides may regulate neuropeptide metabolism in the brain.  Neuropeptides. 1982;  2 169-173
• 3 LaBella F S, Geiger J D, Glavin G B. Administered peptides inhibit the degradation of endogenous peptides. The dilemma of distinguishing direct from indirect effects.  Peptides. 1985;  6 645-660
• 4 McDermott J R, Mantle D, Lauffart B, Kidd A M. Purification and characterization of a neuropeptide-degrading aminopeptidase from human brain.  J Neurochem. 1985;  45 752-759
• 5 O'Cuinn G. Peptide metabolism in cytoplasm of brain cells.  Biochem Soc T. 1998;  26 279-291
• 6 Sladek C D, Blair M L, Chen Y-H, Rockhold R W. Vasopressin and renin response to plasma volume loss in spontaneously hypertensive rats.  Am J Physiol. 1986;  250 H443-H452
• 7 Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.  Anal Biochem. 1976;  72 248-254
• 8 König J FR, Klippel R A. The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. In: Krieger RE (ed) New York; Krieger Huntington 1963: 24-95
• 9 Cheung H S, Cushman D W. A soluble aspartate aminopeptidase from dog kidney.  Biochim Biophys Acta. 1971;  242 190-193
• 10 Mantle M. Comparison of soluble aminopeptidases in human cerebral cortex, skeletal muscle, and kidney tissues.  Clin Chim Acta. 1992;  207 107-118
• 11 Healy D P, Wilk S. Localization of immunoreactive glutamyl aminopeptidase in rat brain. Distribution and correlation with angiotensin II.  Brain Res. 1993;  606 295-303
• 12 Zini S, Fournie-Zaluski M C, Chauvel E, Roques B P, Corvol P, LlorensCortes C. Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release.  Proc Natl Acad Sci USA. 1996;  93 11 968-11 973
• 13 Zini S, Masdehors P, Lenkei Z, Fournie-Zaluski M C, Roques B P, Corvol P, LlorensCortes C. Aminopeptidase A: distribution in rat brain nuclei and increases activity in spontaneously hypertensive rats.  Neuroscience. 1997;  78 1187-1193
• 14 Wright J W, Krebs L T, Stobb J W, Harding J W. The angiotensin IV system: functional implications.  Front Neuroendocrinol. 1995;  16 23-52
• 15 Wright J W, Harding J W. Brain angiotensin receptors subtypes in the control of physiological and behavioral responses.  Neurosci Biobehav Rev. 1994;  18 21-53
• 16 Saavedra J M. Brain and pituitary angiotensin in the central nervous system.  Endocr Rev. 1992;  13 329-380
• 17 Bunnemann B, Fuxe K, Bjelke B, Ganten D. The brain renin-angiotensin system and its possible involvement in volume transmission. In: Fuxe K, Agnati LF (eds) Volume transmission in the brain: Novel mechanisms for neural transmission. New York; Raven Press 1991: 131-158
• 18 Wolf G, Wenzel U, Assamann K JM, Stahl R AK. Renal expression of aminopeptidase A in rats with two-kidney, one-clip hypertension.  Nephrol Dial Transpl. 2000;  15 1935-1942
• 19 Ramírez-Expósito M J, Martínez J M, Prieto I, Alba F, Ramírez M. Comparative distribution of glytamyl and aspartyl aminopeptidase activities in mouse organs.  Horm Metab Res. 2000;  32 161-163
• 20 Ahmad S, Ward P E. Role of aminopeptidase activity in the regulation of the pressor activity of circulating angiotensins.  J Pharmacol Exp Ther. 1990;  252 643-650
• 21 Zini S, Demassey Y, FournieZaluski M C, Bischoff L, Corvol P, LlorensCortes C, Sanderson P. Inhibition of vasopressinergic neurons by central injection of a specific aminopeptidase A inhibitor.  Neuro Report. 1998;  9 825-828
• 22 Palmieri F E, Bausback H H, Ward P E. Metabolism of vasoactive peptides by vascular endothelium and smooth muscle aminopeptidase M.  Biochem Pharmacol. 1989;  38 173-180
• 23 Bausback H H, Ward P E. Degradation of low molecular weight opioid peptides by vascular plasma membrane aminopeptidase M.  Biochim Biophys Acta. 1986;  882 437-444
• 24 Malfroy B, Kado-Fong M, Gros C, Giros B, Schwarte J C, Helmiss R. Molecular cloning and aminoacid sequence of rat kidney aminopeptidase M: a member of superfamily of zinc metallopeptidases.  Biochem Biophys Res Commun. 1989;  161 236-241
• 25 Tonelli L, Chiaraviglio E. Dopaminergic neurons in the zona incierta modulate ingestive behavior in rats.  Physiol Behav. 1995;  58 725-729
• 26 Denton D, Shade R, Zamarippa F, Egan G, Blair-West J, McKinley M, Lancaster J, Fox P. Neuroimaging of genesis and satiation of thirst and an interceptor-driven theory of origins of primary consciousness.  Proc Natl Acad Sci. 1999;  96 5304-5309
• 27 Ward P E, Benter I F, Dick L, Sherwin W. Metabolism of vasoactive peptides by plasma and purified renal aminopeptidase M.  Biochem Pharmacol. 1990;  40 1725-1732
• 28 Fitzismos J T. Angiotensin, thirst, and sodium appetite.  Physiol Rev. 1998;  78 583-686
• 29 Réaux A, de Mota N, Zini S, Cadel S, FournieZaluski M C, Roques B P, Corvol P, LlorensCortes C. PC 18, a specific aminopeptidase N inhibitor, induces vasopressin release by increasing the half life of brain angiotensin III.  Neuroendocrinology. 1998;  69 370-376
• 30 Batt C M, Jensen L L, Harding J W, Wright J W. Microinfusion of aminopeptidase M into the paraventricular nucleus of the hypothalamus in normotensive and hypertensive rats.  Brain Res Bull. 1996;  39 235-240
• 31 Wright J W, Hamilton T A, Harding J W. Anomalous effects of losartan on aminopeptidase-induced reductions of blood pressure in SHR.  Brain Res Bull. 1995;  36 169-174
• 32 Gomez S, Gluschankof P, Lepage A, Cohen P. Relationship between endo- and exopeptidases in a processing enzyme system: activation of an endoprotease by the aminopeptidase B-like activity in somatostatin-28 convertase.  Proc Natl Acad Sci USA. 1988;  85 5468-5472
• 33 Oliveira S M, Freitas J O, Alves K B. Basic aminopeptidase from rabbit kidney: Purification and partial characterization.  Braz J Med Biol Res. 1996;  29 1437-1439
• 34 Häussinger D, Hallbrucker C, von Dahl S, Decker S, Schweizer U, Lang F, Gerok W. Cell volume is a major determinant of proteolysis control in liver.  FEBS. 1991;  1 70-72
• 35 Finn P J, Plank L D, Clark M A, Connolly A B, Hill G. Progressive cellular dehydration and proteolysis in critically ill patients.  Lancet. 1996;  9 654-656
• 36 Stoll B, Gerok W, Lang F, Häussinger D. Liver cell volume and synthesis.  Biochem J. 1992;  287 217-222