Histamine reduces flash sensitivity of on ganglion cells in the primate retina.

PURPOSE. In Old World primates, the retina receives input from histaminergic neurons in the posterior hypothalamus. They are a subset of the neurons that project throughout the central nervous system and fire maximally during the day. The contribution of these neurons to vision, was examined by applying histamine to a dark-adapted, superfused baboon eye cup preparation while making extracellular recordings from peripheral retinal ganglion cells. METHODS. The stimuli were 5-ms, 560-nm, weak, full-field flashes in the low scotopic range. Ganglion cells with sustained and transient ON responses and two cell types with OFF responses were distinguished; their responses were recorded with a 16-channel microelectrode array. RESULTS. Low micromolar doses of histamine decreased the rate of maintained firing and the light sensitivity of ON ganglion cells. Both sustained and transient ON cells responded similarly to histamine. There were no statistically significant effects of histamine in a more limited study of OFF ganglion cells. The response latencies of ON cells were approximately 5 ms slower, on average, when histamine was present. Histamine also reduced the signal-to-noise ratio of ON cells, particularly in those cells with a histamine-induced increase in maintained activity. CONCLUSIONS. A major action of histamine released from retinopetal axons under dark-adapted conditions, when rod signals dominate the response, is to reduce the sensitivity of ON ganglion cells to light flashes. These findings may relate to reports that humans are less sensitive to light stimuli in the scotopic range during the day, when histamine release in the retina is expected to be at its maximum.

Population and molecular evolution studies on the Melanocortin 1 receptor locus implicate its role in human pigmentation variation

Human pigmentation is a complex trait with the observed variation caused by the varied production of eumelanin (brown/black melanins) and phaeomelanin (red/yellow melanins) by the melanocytes. The melanocortin 1 receptor (MC1R), a G protein-coupled receptor expressed in the melanocytes, is a regulator eu- and phaeomelanin synthesis, and MC1R mutations causing skin and coat color changes are known in many mammals. To understand the role of MC1R in human pigmentation variation, I have sequenced the MC1R gene in 121 individuals sampled from world populations. In addition, I have sequenced the MC1R gene in common and pygmy chimpanzees, gorilla, orangutan, and baboon to study the evolution of MC1R and to infer the ancestral human MC1R sequence. The ancestral MC1R sequence is observed in all 25 African individuals studied, but at lower frequencies in the other populations examined, especially in East and Southeast Asians. The Arg163Gln variant is absent in the Africans studied, almost absent in Europeans, and at a low frequency in Indians, but is at an exceptionally high frequency (70%) in East and Southeast Asians. To further evaluate the role of MC1R variants in human pigmentation variation, I have combined these molecular evolution and population studies with functional assays on MC1R variants and primate MC1Rs. ^

CHARACTERIZATION AND COMPARISON OF SUBHUMAN PRIMATE AND HUMAN TYPE C RETROVIRAL GENE PRODUCTS

The viral specific precursor polyproteins of simian sarcoma/simian associated virus (SiSV/SiAV), baboon endogenous viruses (BaEV), and three human isolate retroviruses, have been analyzed by radioimmunoprecipitation and tryptic peptide mapping. Cells infected with the BaEV isolates are characterized by identical precursor polyproteins: gPr80-85('env), Pr70-71('gag), and Pr65-67('gag). By tryptic digest mapping, m7-BaEV and 455K-BaEV were shown to be highly related. By comparison, mapping studies showed that BILN-BaEV was less highly related to m7-BaEV than was 455K-BaEV. Chase-incubated cells infected with BaEV also contained a stable, p28-related polyprotein termed P72('gag). This polyprotein appeared to arise by posttranslational modification of Pr70-71('gag). Tryptic digest mapping of BaEV and HL23V precursor polyproteins suggested that the BaEV-like component of HL23V was more closely related to m7-BaEV than to 455K-BaEV or BILN-BaEV.^ The intracellular precursor polyproteins of SiSV(SiAV) and gibbon ape leukemia virus (GaLV) were compared to the intracellular proteins of the human retrovirus isolates, HL23V, HEL12V, and A1476V. Cells infected with SiSV(SiAV) were characterized by polyproteins Pr200('gag-pol), gPr80('env), Pr80('gag), pr60('gag), and Pr40('gag). We have found that the human isolates are identical to true SiAV with regard to the size and structure of their precursor polyproteins. Both gPr80('env) and Pr60('gag) of SiAV were identical by tryptic peptide mapping to the respective proteins from the three human retroviral isolates examined. We have also shown that these viruses differ significantly from each of the GaLV isolates studied. Since SiAV differs substantially from any known GaLV isolate, we feel that it is unlikely that SiAV is a subtype of GaLV which exists today in the gibbon gene pool. The experimental evidence suggests that SiAV may be an exogenous human retrovirus that was transmitted originally into the human gene pool in the distant past by cross-species infection with GaLV(,SF) or with the GaLV(,SF) progenitor virus. It is, therefore, quite possible that SiAV expression in the pet woolly monkey arose from a recent infection of that monkey with SiAV from humans.^