We have studied the interaction between some heavy metal ions, as compared with earth alkali ions, and calmodulin, a tissue protein which binds Ca2+ and mediates some of its effects. 1. Calmodulin dependent phosphodiesterase was activated with Pb2+, Ca2+, Sr2+, Ba2+, and Cd2+ (EC50 about 0.8 microM). The maximal activation achieved decreases in the order given. Hg2+, Sn2+, Fe2+, Cu2+, Ni2+, Bi3+, and Sb3+ up to 20 microM did not activate. 2. Pb2+ can replace Ca2+ with respect to the calmodulin-dependent phosphorylation of brain membranes. With high Pb2+ concentrations, phosphorylation was inhibited. 3. Calmodulin binding to brain membranes was enhanced with concentrations below 10(-4)M in the following order: Pb2+ greater than or equal to Ca2+ approximately Sr2+ greater than Cd2+ greater than Mn2+ greater than Ba2+. In contrast Mg2+, Hg2+, Sn2+, Fe2+, Ni2+, Co2+, and Cu2+ triggered, if at all, a non-saturable binding of calmodulin. 4. In the flow-dialysis, other ions competed with 45Ca2+ binding to calmodulin in the following order: Pb2+ approximately Ca2+ greater than Mn2+, Ba2+, Cd2+, Sr2+. Thus among the ions investigated Pb2+ is a fully potent substitute for Ca2+ in every calmodulin-dependent reaction investigated. Cd2+ is always much less potent. The earth alkali ions Sr2+ and Ba2+ take an intermediate position. It remains to be shown whether calmodulin is merely a storage site for Pb2+, or whether the resulting functional changes play a role in Pb2+ poisoning.

In this prospective, observational study we explored whether A118G single nucleotide polymorphism in the human mu-opioid receptor (MOR) gene could explain the inter-individual differences in opioid analgesic requirements in patients with acute postoperative pain and chronic pain. The frequency of the wild-type A118 MOR (major) and variant G118 MOR (minor) alleles in the subjects with chronic, noncancer pain (n = 121) and opioid-naïve subjects with acute postoperative pain (n = 101), serving as the control group, were examined. The relationships among the A118G MOR genotype, opioid requirements, and the numerical pain score were analyzed in both groups. The frequency of the minor allele was significantly lower in the subjects with chronic pain when compared with the group with acute postoperative pain (0.079 versus 0.158; P = 0.009 by chi2 test). No statistically significant association was observed between the presence of A118G MOR polymorphism and the average postoperative pain score or the doses of morphine used in the immediate postoperative period. In the high-quartile, opioid utilization, chronic pain patients, the homozygotic carriers of the major allele required significantly higher opioid dose than did the carriers of the minor allele. The results indicate that although the presence of the minor allele does not appear to affect opioid analgesic use in acute postoperative pain, the minor allele is less common in chronic pain patients, especially in those requiring higher doses of opioid analgesics.

Background: A family history has been established as a risk factor for postoperative nausea and vomiting (PONV), but the identities of susceptibility genes remain unknown. The goal of this study was to identify the genetic loci that may contribute to PONV susceptibility in an adult population. Methods:The authors performed a genome-wide association study involving pooling of DNA obtained from 122 patients with severe PONV and 129 matched controls. Each pool was hybridized to a single nucleotide polymorphism (SNP) microarray, and probe intensity was used to predict allele frequency. Differences in allele frequency between SNP in the PONV and control groups were ranked after accounting for the pooling error. The highest ranking SNPs were selected for individual genotyping in the subjects from whom the DNA pool was comprised and in the new verification cohort consisting of 208 subjects (104 PONV patients and 104 controls). Results: The authors identified 41 SNP targets showing substantial difference in allelic frequency between pools. These markers were first genotyped in the individual DNA samples from which the pools were comprised. The authors observed evidence for an association between PONV and 19 different loci in the genome. In the separate verification cohort, the association with PONV was observed for four SNPs. This association remained significant after correcting