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NKW 221 S 04 2 '1'tuc r. Ft Iit'!'(m.%c•c•c) I.I:a:.% uc•Al-ti .S.A.. l.Nc. June 10, 1977 )~,m;1RJjtDUt1 / TO: Drs. &ing, Y.ockett, Sor.imers and Stone and Feldman FROM: W. U. Gardner SUBJECT: Acolication 1058R1. JakoL Schmidt, M.D., Ph.D., Denartsnent of Biochemistry, State University of New York, Stony Brook. "Central Nicotinic Receptors." During the first year the grant was apprcved for S46,395. ;59,390 had been reauestec from %ove ber 1, 1976 throuah October 31, 1077. The time of commitmer.t was limited to one year because of some buestion about t..=-__~ ~ the efficacy of affinity chromatooranhy in the purification of the binding material. Procress. Durino the past six *:dntas he has conpleted a survey of the distri:^ution of the EaTYX bindinc in different Larts of the centsal nervous svste^ and different orcans and tissues including sympathetic and dorsal root aanclia. Striated r.+uscle has also binding sites. This is an aprroach that may associate ACh-nicotinic hindina sites with EuTX sites. P.Ch-nicotinic drugs caused a disassociation of the BuTX complexes in the brain but not in the muscle sites. Last year it was thought that BuTX was irreversibly bound. Some progress has been made on the affinity PC chromato- graphy and also with the autoradioaraphic localization at the light microscopic level. The bindinc of the toxin in dorsal root ganglia and in the trice:ginal aanglia is hard to rationalize with a neurotransmitter function. I do not know the evidence for the statement "the oresence of nicotinic-HCh rece_ntors in extrasynaatic regions of sensory fibers is well established." Proiection. Continue on with the isolation and Durification of the toxin binding material, determine whether it is identical to the ACh-N binding material an3 to determing why the material does not inhibit synaptic trans:nission in the central nervous svstem. i•:nen Don Ford comes aboard I think that he should do a site visit. He requests a two-month extension ($11,119) which is more than proratincJ. I would favor support at the saine level for November and December. He requests $81,107 for 1978. $17,000 is for a camma counter'. The cnunter that they have been using is moving away from them. Dr. Stephen Hunt ~ees the electron microscopist and autoradiofp?ratiherli5 using 1V5I-BuT:{. Dr. 7 Marchand is working with the affinity chromatogranhy. He has an NTH application scheduled to start 1/1/78 for much the same type of work. At present he lists grants totaling $20,500 in addition to the CTR grant. R'. U. Gardner r:U~;:eY: