Tonin expression in the rat brain and tonin-mediated central production of angiotensin II.
Tonins are serine proteinases mainly found in the rat submandibular gland, which are capable of generating the pressor octapeptide angiotensin II (Ang II) not only from the classical substrate angiotensin I but also from the synthetic tetradecapeptide (AG(1-14)) and from angiotensinogen. In this work, tonin expression levels were evaluated in astrocytes and brain areas of the rat. By two different techniques (ribonuclease protection assay and reverse transcription-polymerase chain reaction), we could verify the presence of tonin mRNA in astrocytes and in the thalamus of the rat brain. Sequencing of the amplified brain cDNA determined it to be identical to that found in the submandibular gland. Central microinjection of tonin produced a transient (10-20 min) elevation of blood pressure and heart rate and induced water and saline intake within the first 10 min after injection. Urinary volume and salt excretion increased within 7 h after tonin injection. These effects were partially blocked by previously administered losartan, indicating that tonin effectively induced a central Ang II formation. Our data suggest that tonin may be an alternative pathway to Ang II generation in the brain and could participate in the physiological effects exerted by Ang II such as water and saline intake and blood pressure elevation.
Araujo
Ronaldo C
RC
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Lima
Mercia P
MP
Lomez
Eliane S L
ES
Bader
Michael
M
Pesquero
Joao B
JB
Sumitani
Marie
M
Pesquero
Jorge L
JL
D000199:Actins / Q000096:biosynthesis; D000804:Angiotensin II / Q000096:biosynthesis*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D004327:Drinking Behavior / Q000187:drug effects; D007276:Injections, Intraventricular; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D023282:Nuclease Protection Assays; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000494:pharmacology*; D020840:Tissue Kallikreins / Q000096:biosynthesis* / Q000494:pharmacology*; D014563:Urodynamics / Q000187:drug effects
D000199:Actins; D000804:Angiotensin II; D012697:Serine Endopeptidases; C117017:tonin; D020840:Tissue Kallikreins