Mild acute intestinal inflammation induced by DSS can be inhibited by 4-CA and this action is associated with the suppression of COX-2 expression and activity.

Abstract. Interactions between μ-opioid receptor (μOR) and cannabinoid CB 1 receptor (CB 1 R) were examined by morphological and electrophysiological methods. In baby hamster kidney (BHK) cells coexpressing μOR fused to the yellow fluorescent protein Venus and CB 1 R fused to the cyan fluorescent protein Cerulean, both colors were detected on the cell surface; and fluorescence resonance energy transfer (FRET) analysis revealed that μOR and CB 1 R formed a heterodimer. Coimmunoprecipitation and Western blotting analyses also confirmed the heterodimers of μOR and CB 1 R. [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]enkephalin (DAMGO) or CP55,940 elicited K + currents in Xenopus oocytes expressing μOR or CB 1 R together with G protein activated-inwardly rectifying K + channels (GIRKs), respectively. In oocytes coexpressing both receptors, either of which was fused to the chimeric Gα protein G qi5 that activates the phospholipase C pathway, both DAMGO and CP55,940 elicited Ca 2+ -activated Cl − currents, indicating that each agonist can induce responses through G qi5 fused to either its own receptor or the other. Experiments with endogenous G i/o protein inactivation by pertussis toxin (PTX) supported the functional heterodimerization of μOR/ CB 1 R through PTX-insensitive G qi5(m) fused to each receptor. Thus, μOR and CB 1 R form a heterodimer and transmit a signal through a common G protein. Our electrophysiological method could be useful for determination of signals mediated through heterodimerized G protein-coupled receptors.

No abstract

The multiple 5-hydroxytryptamine (5-HT, serotonin) receptor subtypes are distinguished. In this article, we described mainly the 5-HT4 receptor of four subtypes of functional 5-HT receptors, 5-HT1, 5-HT2, 5-HT3, and 5-HT4, recognized in the gastrointestinal tract. In-vivo microdialysis experiments determined that activation of the 5-HT4 receptor stimulated intestinal motor activity associated with a local increase in acetylcholine (ACh) release from the intestinal cholinergic neurons in the whole body of dogs. The 5-HT4 receptor-mediated response of ACh release in the antral, corporal, and fundic strips isolated from guinea pig stomach corresponds to the presence of 5-HT4 receptor in the myenteric plexus. In-vitro receptor autoradiograms of the stomach and colon indicate that the distribution of 5-HT4 receptors in human tissues is similar to that in the guinea pig, although density of 5-HT4 receptors in the myenteric plexus of human tissues is lower than that in guinea pig tissues. The 5-HT4 receptors located in the myenteric plexus may participate in gastrointestinal motility, and thus the 5-HT4 agonists and antagonists may be available for treatment of dysfunction of gastrointestinal motility.

We investigated the inactivation process of macroscopic cardiac L-type Ca(2+) channel currents using the whole cell patch-clamp technique with Na(+) as the current carrier. The inactivation process of the inward currents carried by Na(+) through the channel consisted of two components >0 mV. The time constant of the faster inactivating component (30.6 +/- 2.2 ms at 0 mV) decreased with depolarization, but the time constant of the slower inactivating component (489 +/- 21 ms at 0 mV) was not significantly influenced by the membrane potential. The inactivation process in the presence of isoproterenol (100 nM) consisted of a single component (538 +/- 60 ms at 0 mV). A protein kinase inhibitor, H-89, decreased the currents and attenuated the effects of isoproterenol. In the presence of cAMP (500 microM), the inactivation process consisted of a single slow component. We propose that the faster inactivating component represents a kinetic of the dephosphorylated or partially phosphorylated channel, and phosphorylation converts the kinetics into one with a different voltage dependency.