Coupling of M3 acetylcholine receptor to Gq16 activates a natriuretic peptide receptor guanylyl cyclase

Gustavo Bruges, Adolfo Borges, Sinai Sánchez De Villarroel, Itala Lippo De Bécemberg, Gisela Francis De Toba, Fabiola Pláceres, Ramona González De Alfonzo, Marcelo J. Alfonzo

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Muscarinic activation of tracheal smooth muscle (TSM) involves a M3AChR/heterotrimeric-G protein/NPR-GC coupling mechanism. G protein activators Mastoparan (MAS) and Mastoparan-7 stimulated 4- and 10-fold the NPR-GC respectively, being insensitive to PTX and antibodies against Gαi/o subfamily. Muscarinic and MAS stimulation of NPR-GC was blocked by antibodies against C-terminal of Gαq16, whose expression was confirmed by RT-PCR. However, synthetic peptides from C-terminal of Gαq15/16 stimulated the NPR-GC. Coupling of αq16 to M3AChR is supported by MAS decreased [3H]QNB binding, being abolished after M3AChR-4-DAMP-alkylation. Anti-i3M3AChR antibodies blocked the muscarinic activation of NPR-GC, and synthetic peptide from i3M3AChR (M3P) was more potent than MAS increasing GTPγ [35S] and decreasing the [3H]QNB activities. Coupling between NPR-GC and Gαq16 was evaluated by using trypsin-solubilized-fraction from TSM membranes, which displayed a MAS-sensitive-NPR-GC activity, being immunoprecipitated with anti-Gαq16, also showing an immunoreactive heterotrimeric-G-β- subunit. These data support the existence of a novel transducing cascade, involving Gαq16βγ coupling M3AChR to NPR-GC.

Original languageEnglish
Pages (from-to)189-216
Number of pages28
JournalJournal of Receptors and Signal Transduction
Volume27
Issue number2-3
DOIs
StatePublished - Mar 2007
Externally publishedYes

Keywords

  • G proteins
  • Guanylyl cyclases
  • Muscarinic receptors
  • NPR-B
  • Tracheal smooth muscle

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