The m 1maln prion protein (PrPC) is a cellular protein of unknown function, an altered isoform of which (PrPs) is a component of the infectious particle (prion) thought to be responsible for spongiform encephalopathies in humans and animals. We report here the isolation of a cDNA that encodes a chicken protein that is homologous to PrPc. This chicken prion-like protein (ch-PrLP) is identical to the mouse PrP at 33% of its amino acid positions, including an uninterrupted stretch of 24 identical residues, and it displays the saw structural domains. In addition, ch-PrLP, like its mamain counterpart, is attached to the cell surface by a glycosylphosphatidylinositol anchor. We find that ch-PrLP is the major protein in preparations of an acetylcholine receptor-inducing activity that has been purified >1O'-fold from brain on the basis of its ability to stimulate synthesis of nicotinic receptors by cultured myotubes. The ch-PrLP gene is expressed in the spinal cord and brain as early as embryonic day 6; and in the spinal cord, the protein appears to be concentrated in motor neurons. Our results therefore raise the possibility that prion proteins serve normally to regulate the chemoreceptor number at the neuromuscular junction and perhaps in the central nervous system as well.

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Summary. Melittin, an activator of phospholipase (PL) A-2, increased the outputs of prostaglandin (PG) F-2\g=a\and 6-keto-PGF-1\g=a\, but not of PGE-2, from Day-7 guineapig uterus superfused in vitro. Reducing the extracellular calcium concentration (by omitting calcium chloride from the superfusing fluid) partially inhibited the stimulatory effect of melittin on uterine PG production. (an intracellular calcium antagonist) completely prevented the stimulation of PGF-2\g=a\and 6-keto-PGF-1\g=a\ output by melittin, although the production of both PGs tended to increase after stopping the melittin and TMB-8 treatments. TMB-8 also inhibited the increases in outputs of PGF\x=req-\ 2\g=a\,6-keto-PGF-1\g=a\ and PGE-2 and prevented contraction of the uterus induced by exogenous PLA-2. Trifluoperazine (a calmodulin antagonist) had no inhibitory effect on the increases in outputs of PGF-2\g=a\and 6-keto-PGF-1\g=a\ produced by melittin; it potentiated the stimulatory effect of melittin on 6-keto-PGF-1\g=a\ output and allowed melittin to increase PGE-2 output. When melittin was applied twice to the superfused uterus with an interval of 1 h between each treatment, partial refractoriness of the responses to melittin was seen: the magnitudes of the increases in PGF-2\g=a\and 6\ x =r eq-\ keto-PGF-1\g=a\ outputs were 40\p=n-\50%less after the second treatment than after the first treatment. These results show that melittin stimulates the synthesis of PGF-2\g=a\and PGI-2 (measured as 6-keto-PGF-1\g=a\) in guinea-pig uterus by mechanisms which are calcium dependent. The results are compatible with there being a protein of similar functional activity to melittin in the guinea-pig uterus, which may be involved in the stimulation of endometrial PGF-2\g=a\ synthesis.

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