The recent progress in research on effects of anesthetics and analgesics on G protein-coupled receptors

Abstract

The exact mechanisms of action behind anesthetics and analgesics are still unclear. Much attention was focused on ion channels in the central nervous system as targets for anesthetics and analgesics in the 1980s. During the 1990s, major advances were made in our understanding of the physiology and pharmacology of G protein coupled receptor (GPCR) signaling. Thus, several lines of studies have shown that G protein coupled receptors (GPCRs) are one of the targets for anesthetics and analgesics and especially, that some of them inhibit the functions of GPCRs, i.e,, muscarinic receptors and substance P receptors. However, these studies had been focused on only G(q) coupled receptors. There has been little work on G(s)- and G(i)-coupled receptors. In the last decade, a new assay system, using chimera G(i/o)-coupled receptor fused to Gq(i5), has been established and the effects of anesthetics and analgesics on the function of G(i)-coupled receptors is now more easily studied. This review highlights the recent progress of the studies regarding the effects of anesthetics and analgesics on GPCRs.

Molecular recognition of ketamine by a subset of olfactory G protein–coupled receptors

“…Indeed, ketamine has antidepressant activity (2), raising the possibility that it interacts in the central nervous system (CNS) with heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs), a receptor superfamily frequently targeted by antidepressants and other psychotherapeutics (3–5). This possibility is consistent with the demonstration that ketamine binds to opioid and muscarinic receptors (6). …”

The sodium leak channel, NALCN, in health and disease

“…However, the action mechanisms of GAs are not completely understood. Several ion channels and GPCRs are affected by these compounds (reviewed in Chau, 2010; Minami and Uezono, 2013). Of interest, it is known for a long time that GAs such as halothane, hyperpolarize neurons by acting on the potassium currents likely by activating two-pore potassium channels (Patel et al, 1999; Gruss et al, 2004; Liu et al, 2004).…”

Intravenous lidocaine to treat postoperative pain

“…It is also important to highlight that preferential blockade for inactivated sodium channels promoted by lidocaine assures that only hyperexcitable neuron channels are blocked, such as those with post-nervous injury ectopic activity 35 . However, for nociceptive pain results are in disagreement with regard to such preferential block 36,37,39 . Still with regard to the analgesic effect, it seems to be dose-dependent, and 5mg/kg for a period of 30 minutes has promoted more consistent analgesic response 36 .…”

“…This local anesthetic also seems to indirectly block NMDA receptors [34][35][36] by inhibiting protein kinase C (PKC) 35 , thus highly influencing postoperative hyperalgesia and tolerance to opioids 10,35 . In addition, this drug through its action on RAPG 37 , interferes with sensitization, lysosomal degranulation of neutrophils, production of oxygen free radicals and cytokines production by macrophages and glial cells providing anti-inflammatory action 14,37,38 .…”