Tonin, a serinoproteinase, is capable of releasing angiotensin II by the
hydrolysis of Phe8-His9 bond in the angiotensinogen, angiotensin I and synthetic
peptides corresponding to the N-terminal portion of angiotensinogen. Tonin is able to
hydrolyze beta-lipotropic hormone releasing an opiate-like segment. It is capable of
degrading adrenocorticotropic hormone, substance P but not bradykinin.
Hydrolysis of Phe.His bond depends on a minimum sequence involving residues
Ile.His.Pro.Phe.His.Leu. Tonin activity is present in human and rat tissues. In the rat,
tonin is present in various tissues including kidney, brain and heart, and the activity
levels vary according to age and sex being higher in males. Tonin is released into
bloodstream and saliva after beta-adrenergic stimulation. There is evidence that tonin is
involved in blood pressure control and participates in the hydromineral balance.
Intracerebroventricular injection of tonin induces salt appetite and water intake and
increases urinary volume and blood pressure. TGM(rTon), a transgenic mouse that
expresses rat tonin, presents increased blood pressure. The levels of angiotensin II in
the plasma are increased in TGM(rTon) and the AT1 receptors desensitized when
compared to the wild type. A significant increase in the plasmatic and a decrease in
urinary sodium were observed in TGM(rTon), suggesting alterations in the renal
function. Induction of cardiac hypertrophy by isoproterenol injection in rats showed
that tonin may be involved in this process. TGM(rTon) presents resistance to develop
isoproterenol-induced hypertrophy. The molecular basis for the hypertrophy resistance is to be determined. These results lead us to conclude that tonin, an angiotensin II
liberating enzyme may represent an alternative pathway with effects on the renal and
cardiovascular systems.
Keywords: Angiotensin I, Angiotensin II, Angiotensinogen, Antinociceptive
effect, Blood pressure, Converting enzyme, Heart, Hypertension, Hypertrophy
resistance, Isoproterenol, Renin, Serine proteinase, Tonin, Transgenic mouse,
Water intake.
