title: Angiotensin (5-8) modulates nociception at the rat periaqueductal gray via the NO-sGC pathway and an endogenous opioid.
abstract: Angiotensins (Angs) modulate blood pressure, hydro-electrolyte composition, and antinociception. Although Ang (5-8) has generally been considered to be inactive, we show here that Ang (5-8) was the smallest Ang to elicit dose-dependent responses and receptor-mediated antinociception in the rat ventrolateral periaqueductal gray matter (vlPAG). Ang (5-8) antinociception seems to be selective, because it did not alter blood pressure or act on vascular or intestinal smooth muscle cells. The non-selective Ang-receptor (Ang-R) antagonist saralasin blocked Ang (5-8) antinociception, but selective antagonists of Ang-R types I, II, IV, and Mas did not, suggesting that Ang (5-8) may act via an unknown receptor. Endopeptidase EP 24.11 and amastatin-sensitive aminopeptidase from the vlPAG catalyzed the synthesis (from Ang II or Ang III) and inactivation of Ang (5-8), respectively. Selective inhibitors of neuronal-nitric oxide (NO) synthase, soluble guanylyl cyclase (sGC) and a non-selective opioid receptor (opioid-R) inhibitor blocked Ang (5-8)-induced antinociception. In conclusion, Ang (5-8) is a new member of the Ang family that selectively and strongly modulates antinociception via NO-sGC and endogenous opioid in the vlPAG.
authors.affiliation: Department of Psychology, FFCLRP University of São Paulo, Ribeirão Preto 14049-901, SP, Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Guethe
authors.forename: A
authors.initials: A
authors.lastname: Pelegrini-da-Silva
authors.forename: K G
authors.initials: KG
authors.lastname: Borelli
authors.forename: M A
authors.initials: MA
authors.lastname: Juliano
authors.forename: G G
authors.initials: GG
authors.lastname: Pelosi
authors.forename: J B
authors.initials: JB
authors.lastname: Pesquero
authors.forename: C L M
authors.initials: CL
authors.lastname: Silva
authors.forename: F M A
authors.initials: FM
authors.lastname: Corrêa
authors.forename: F
authors.initials: F
authors.lastname: Murad
authors.forename: W A
authors.initials: WA
authors.lastname: Prado
authors.forename: A R
authors.initials: AR
authors.lastname: Martins
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects*; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012504:Saralasin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D000071756:Soluble Guanylyl Cyclase; D013722:Teprotide / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D018847:Opioid Peptides; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D000803:Angiotensin I; D013722:Teprotide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D012504:Saralasin