Abstract:The hypothesis of these studies is that ligand efficacy at the neuronal CB1 receptor is dependent on the ratio of ligand affinities for the active and inactive states of the receptor. Agonist efficacy was determined in rat cerebellar membranes using agonist-induced guanosine 5Ј-O-(3-[35 S]thiotriphosphate) binding; efficacy was variable among the CB1 agonists examined. Ligand affinities for the active and inactive state of the CB1 receptor were determined by competition with [ 3 H]CP55940 and [3 H]SR141716A in the presence of 5Ј-guanylylimidodiphosphate, respectively. All of the agonists investigated had a higher affinity for the active state than the inactive state. The fraction of CB1 receptors in the active state at a maximally effective concentration was calculated for each agonist and was found to correlate significantly with agonist efficacy. These studies demonstrate that the CB1 receptor of the cerebellum can assume an active conformation in the absence of agonist and that the variability in efficacy among CB1 receptor agonists can be explained by the relative affinities of these ligands for the CB1 receptor in the active and inactive states. Key Words: Anandamide -CP55940 -⌬ 9 -Tetrahydrocannabinol-HU210 -Inverse agonistMarijuana-N-Arachidonylethanolamine -SR141716A-WIN 55212-2.

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Complement protein levels and C7 hemolytic activity were measured in four individuals following anesthesia and surgery, and in a group of 20 patients with inflammatory diseases. Seven of the eight complement components studied characteristically were elevated, most dramatically C1s and C3PA. Elevation of C1s often was greater than elevation of C1q, displaying an independent variation of C1s and C1q in both postoperative and inflammatory disease patient groups. The major increases of C components were seen subsequent to the peak C-reactive protein response, as was the occurrence of the ‘reactor state’, a propensity to formation of C56 which surprisingly was associated with increased levels of C7. Levels of properdin frequently were reduced postoperatively. It is concluded that multiple complement components, with the notable exception of properdin, respond as acute phase reactants which are elevated and changed in proportion postoperatively and during inflammatory disease.

The association of a and /? 2 subunits of tryptophan synthetase from Escherichia coli and Salmonella typhimurium in homologous and heterologous combinations was studied by sucrose density gradient centrifugation. Under conditions allowing for optimal association of subunits derived from the same source, subunit association in the mixture E. coli a-S. typhimurium /? 2 was weaker than normal while in the reciprocal combination of S. typhimurium