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00925njm 22002777a 4500 dc Borroto Escuela, Dasiel Óscar author García-Negredo, Gloria author Garriga, Pere author Fuxe, Kjell author Ciruela, Francisco author 2010-04-14 Besides some pharmacological, biochemical and biophysical evidences support the contention that muscarinic acetylcholine receptors can form homo- and heterodimers, the existence of specific M3 and M5 muscarinic receptors oligomers in living cells is a new concept. Interestingly, this phenomenon might have relevance in lymphocytic cholinergic function since both T- and B-cells naturally express high levels of these two receptor subtypes. Here, by means of co-immunoprecipitation and bioluminescence resonance energy transfer methods we demonstrated that M3 and M5 muscarinic receptors could form constitutive homo- and heterodimers in transiently transfected HEK-293T cells. Interestingly, this receptor-receptor interaction was unaltered by carbachol treatment but it was affected by the expression of a peptide corresponding to a portion of the third intracellular loop of the M5 muscarinic receptor. In addition, the same peptide was able to abrogate the carbachol-induced mitogen-activated protein kinase phosphorylation and the carbachol-enhanced PHA-induced IL-2 production in derived lymphocytic T cells. Overall, these results suggest that the third intracellular loop of the M5 muscarinic receptor might play a regulatory role in receptor function and heteromerization, thus providing the molecular framework for a potential cholinergic-based therapeutic intervention of the immune system. Dasiel O. Borroto-Escuela, Gloria García-Negredo, Pere Garriga, Kjell Fuxe, Francisco Ciruela, The M5 muscarinic acetylcholine receptor third intracellular loop regulates receptor function and oligomerization, Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Volume 1803, Issue 7, 2010, Pages 813-825, ISSN 0167-4889, https://doi.org/10.1016/j.bbamcr.2010.04.002. (https://www.sciencedirect.com/science/article/pii/S0167488910001084) 0167-4889 https://doi.org/10.5281/zenodo.13860037 https://hdl.handle.net/10630/45001 10.1016/j.bbamcr.2010.04.002 Proteínas G Receptores colinérgicos Neurorreceptores The M5 muscarinic acetylcholine receptor third intracellular loop regulates receptor function and oligomerization