Peptides
-
The involvement of the μ-opioid receptor subtypes on the presynaptic or postsynaptic inhibition of spinal pain transmission was characterized in ddY mice using endomorphins. Intrathecal treatment with capsaicin, N-methyl-d-aspartate (NMDA) or substance P elicited characteristic nociceptive behaviors that consisted primarily of vigorous biting and/or licking with some scratching. Intrathecal co-administration of endogenous μ-opioid peptide endomorphin-1 or endomorphin-2 resulted in a potent antinociceptive effect against the nociceptive behaviors induced by capsaicin, NMDA or substance P, which was eliminated by i.t. co-administration of the μ-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP). ⋯ In contrast, the antinociceptive effect of endomorphin-2 was significantly suppressed by i.t.-co-administration of D-Pro2-endomorphin-2 but not D-Pro2-endomorphin-1 on capsaicin-, NMDA- or substance P-elicited nociceptive behaviors. Interestingly, regarding substance P-elicited nociceptive behaviors, the antinociceptive effect of endomorphin-1 was significantly suppressed by i.t.-co-administration of another μ2-opioid receptor antagonist, Tyr-D-Pro-Trp-Gly-NH2 (D-Pro2-Tyr-W-MIF-1), but not D-Pro2-endomorphin-1 or D-Pro2-endomorphin-2. The present results suggest that the multiple μ-opioid receptor subtypes are involved in the presynaptic or postsynaptic inhibition of spinal pain transmission.
-
The renin-angiotensin system (RAS) regulates skeletal muscle insulin sensitivity through different mechanisms. The overactivation of the ACE (angiotensin-converting enzyme)/Ang (angiotensin) II/AT1R (Ang II type 1 receptor) axis has been associated with the development of insulin resistance, whereas the stimulation of the ACE2/Ang 1-7/MasR (Mas receptor) axis improves insulin sensitivity. The in vivo mechanisms by which this axis enhances skeletal muscle insulin sensitivity are scarcely known. ⋯ In a similar manner, captopril (an ACE inhibitor) enhanced insulin-induced glucose uptake and this effect was blocked by the MasR antagonist A-779. Our results show for the first time that rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis of the RAS, and Ang 1-7 improves insulin sensitivity by enhancing insulin-stimulated glucose uptake in rat skeletal muscle in vivo. Thus, endogenous (systemic and/or local) Ang 1-7 could regulate insulin-mediated glucose transport in vivo.