Solomon H. Snyder MD, DSc, DPhil (Hon Causa)

Professor of Neuroscience

For a more complete list of publications, click here.



Opiate Receptors:

The first definitive identification of pharmacologically relevant opiate receptors; differentiation of agonists, antagonists and less addicting mixed agonist-antagonists; detailed localizations in monkey and human brain accounting for opiate-selective influences on pain perception and emotional behavior.

Pert, C. and Snyder, S.H. Opiate receptor: demonstration in nervous tissue. Science 179:1011-1014, 1973.

Kuhar, M.J., Pert, C.B. and Snyder, S.H. Regional distribution of opiate receptor binding in monkey and human brain. Nature 245:447-450, 1973.

Pert, C.B., Pasternak, G. and Snyder, S.H. Opiate agonists and
antagonists discriminated by receptor binding in brain. Science 182:1359-1361, 1973.

Other Neurotransmitter Receptors:

Identification of principal neurotransmitter receptors by ligand binding including glycine, dopamine, serotonin, GABA, -adrenergic, and adenosine sites. Differentiation biochemically and behaviorally of serotonin receptor subtypes. Correlation of antipsychotic actions of neuroleptics with blockade of a subtype of dopamine receptors. Increased dopamine receptors linked to behavioral dopamine supersensitivity following dopamine neuronal lesions and chronic neuroleptic treatment modeling tardive dyskinesia. Demonstration that adenosine receptor blockade mediates behavioral stimulant effects of caffeine.

Young, A.B. and Snyder, S.H. Strychnine binding associated with glycine receptors of the central nervous system. PNAS 70:2832-2836, 1973.

Yamamura, H.I. and Snyder, S.H. Muscarinic cholinergic binding in rat brain PNAS 71:1725-1729, 1974.

Zukin, S.R., Young, A.B. and Snyder, S.H. Gamma-aminobutyric acid binding to receptor sites in the rat central nervous system. PNAS 71:4802-4807, 1974.

Burt, D.R., Enna, S.J., Creese, I. and Snyder, S.H. Dopamine receptor binding in the corpus striatum of mammalian brain. PNAS 72:4655-4659, 1975.

Creese, I., Burt, D.R. and Snyder, S.H. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481-483, 1976.

Burt, D.R., Creese, I. and Snyder, S.H. Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 196:326-328, 1977.

Creese, I., Burt, D.R. and Snyder, S.H. Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity. Science 197:596-598, 1977.

U’Prichard, D.C., Greenberg, D.A., Sheehan, P.P. and Snyder, S.H. Tricyclic antidepressants: therapeutic properties and affinity for -noradrenergic receptor binding sites in the brain. Science 199:197-198, 1978.

U’Prichard, D.C. and Snyder, S.H. Distinct -noradrenergic receptors differentiated by binding and physiological relationships. Life Sciences 24:79- 88, 1979.

Peroutka, S.J. and Snyder, S.H. Multiple serotonin receptors: differential binding of 3H-3-hydroxytryptamine, 3H-lysergic acid diethylamide and 3H-spiroperidol. Mol. Pharmacol. 16:687-699, 1979.

Bruns, R.F., Daly, J.W. and Snyder, S.H. Adenosine receptors in brain membranes: binding of N6-cyclohexyl[3H]adenosine and 1,3-diethyl-8- [3H]phenylxanthine. PNAS 77:5547-5551, 1980.

Peroutka, S.J., Lebovitz, R.M. and Snyder, S.H. Two distinct central serotonin receptors with different physiological functions. Science 212:827-829, 1981.

Snyder, S.H., Katims, J.J., Annau, Z., Bruns, R.F. and Daly, J.W. Adenosine receptors and behavioral actions of methylxanthines. PNAS 78:3260-3264, 1981.

Bruns, R.F., Daly, J.W. and Snyder, S.H. Adenosine receptor binding: structure- activity analysis generates extremely potent xanthine antagonists. PNAS 80:2077-2080, 1983.

Opioid and Other Neurotransmitter Peptides:

Identification of endogenous opioid activity by competition for opiate receptor binding with regional localizations paralleling opiate receptor distribution. Independent isolation and confirmation of enkephalin peptide structures. First histochemical localization of enkephalin neurons in brain corresponding to opiate receptor distribution establishing enkephalins as principal endogenous opiate receptor ligands. Identification and localization of neurotensin, cholecystokinin and bradykinin neurons and receptors. Establishment of bradykinin as an endogenous pain activator. Identification and purification of carboxypeptidase E (enkephalin convertase) as a major neuropeptide processing enzyme.

Snyder, S.H. Opiate receptor in normal and drug altered brain function. Nature 257:185-189, 1973.

Simantov, R. and Snyder, S.H. Morphine-like peptides in mammalian brain: isolation, structure elucidation, and interactions with the opiate receptor. PNAS 73:2515-2519, 1976.

Simantov, R., Kuhar, M.J., Uhl, G.R. and Snyder, S.H. Opioid peptide enkephalin: immunohistochemical mapping in rat central nervous system. PNAS 74:2167-2171, 1977.

Uhl, G.R., Kuhar, M.J. and Snyder, S.H. Neurotensin: immunohistochemical localization in rat central nervous system. PNAS 74:4059-4063, 1977.

Innis, R.B., Correa, F.M., Uhl, G.R., Schneider, B. and Snyder, S.H. Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain. PNAS 76:521-525, 1979.

Larsson, L., Childers, S. and Snyder, S.H. Met- and leu-enkephalin immunoreactivity in separate neurons. Nature 282:407-410, 1979.

Fricker, L.D. and Snyder, S.H. Enkephalin convertase: purification and characterization of a specific enkephalin synthesizing carboxypeptidase localized to adrenal chromaffin granules. PNAS 79:3886-3890, 1982.

Steranka, L.R., Manning, D.C., DeHaas, C.J., Ferkany, J.W., Borosky, S.A., Connor, J.R., Vavrek, R.J., Stewart, J.M. and Snyder, S.H. Bradykinin as a pain mediator: receptors are localized to sensory neurons, and antagonists have analgesic actions. PNAS 85:3245-3249, 1988.

Inositol polyphosphates, IP3 Receptors and Other Messenger Proteins:

Identification of IP3 receptors enriched in brain permitting purification to homogeneity. Demonstration that IP3 binding protein contains the calcium release channel and accounts for fundamental features of cellular calcium disposition such as quantal release. Discovery of high brain levels of immunophilins, neurotrophic and neuroprotective actions of immunophilin ligands including non-immunosuppressant agents in clinical trial for Parkinson’s disease and neuroprotective relief of past prostatectomy erectile dysfunction. Discovery and functional characterization of RAFT (TOR, FRAP) as the protein target of rapamycin. Regulation of IP3 receptors by physiologically bound FKBP12. Discovery of a cell death cycle whereby cytochrome C released by mitochondria augments calcium release from IP3 receptors in apposed endoplasmic reticulum. Discovery that energetic inositol pyrophosphates physiologically pyrophosphorylate proteins. Development of an algorithm detecting intermolecular protein recognition motifs, revealing intermolecular PH domains linking phospholipase Cto TRP calcium channels.

Worley, P.F., Baraban, J.M., Colvin, J. S. and Snyder, S.H. Inositol trisphosphate receptor localization in brain: variable stoichiometry with protein kinase C. Nature 325:159-161, 1987.

Worley, P.F., Baraban, J.M., Supattapone, S., Wilson, V.S. and Snyder, S.H. Characterization of inositol trisphosphate receptor binding in brain: regulation by pH and calcium. J. Biol. Chem. 262:12132-12136, 1987.

Supattapone, S., Worley, P.F., Baraban, J.M. and Snyder, S.H. Solubilization, purification and characterization of an inositol trisphosphate receptor. J. Biol. Chem. 263:1530-1534, 1988.

Ross, C.A., Meldolesi, J., Milner, T.A., Satoh, T., Supattapone, S. and Snyder, S.H. Inositol 1,4,5-trisphosphate receptor localized to endoplasmic reticulum in cerebellar Purkinje neurons. Nature 339:468-470, 1989.

Ferris, C.D., Weisman, H.F., Levine, J.H., Snowman, A.M. and Snyder, S.H. Purified inositol 1,4,5-trisphosphate receptor mediates calcium flux in reconstituted lipid vesicles. Nature 342:87-89, 1989.

Danoff, S.K., Ferris, C.D., Donath, C., Fischer, G.A., Munemitsu, S., Ullrich, A., Snyder, S.H. and Ross, C.A. Inositol 1,4,5-trisphosphate receptors: distinct neuronal and non-neuronal forms derived by alternative splicing differ in phosphorylation. PNAS 88:2951-2955, 1991.

Ferris, C.D., Cameron, A.M., Huganir, R.L. and Snyder, S.H. Quantal calcium release by purified reconstituted inositol 1,4,5-trisphosphate receptors. Nature 356:350-352, 1992.

Ross, C.A., Danoff, S.K. Schell, M.J., Snyder, S.H. and Ullrich, A. Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and differential localization in brain and peripheral tissues. PNAS 89:4265-4269, 1992.

Khan, A.A., Steiner, J.P., Klein, M.G., Schneider, M.F. and Snyder, S.H. IP3 receptor: localization to plasma membrane of T cells and co-capping with the T cell receptor. Science 257:815-818, 1992.

Steiner, J.P., Dawson, T.M., Fotuhi, M., Glatt, C.E., Snowman, A.M., Cohen, N. and Snyder, S.H. High brain densities of the immunophilin FKBP colocalized with calcineurin. Nature 358:584-587, 1992.

Dawson, T.M., Steiner, J.P., Dawson, V.L., Dinerman, J.L., Uhl, G.R. and Snyder, S.H. Immunosuppressant, FK506, enhances phosphorylation of nitric oxide synthase and protects against glutamate neurotoxicity. PNAS 90:9808-9812, 1993.

Sabatini, D.M., Erdjument-Bromage, H., Lui, M., Tempst, P. and Snyder, S.H. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 78:35-43, 1994.

Cameron, A.M., Steiner, J.P., Sabatini, D.M., Kaplin, A.I., Walensky, L.D. and Snyder, S.H. Immunophilin FKBP binding protein associated with inositol 1,4,5- trisphosphate receptor modulates calcium flux. PNAS 92:1784-1788, 1995.

Khan, A.A., Soloski, M.J., Sharp, A.H., Schilling, G., Sabatini, D.M., Li, S-H, Ross, C.A. and Snyder, S.H. Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor. Science 273:503-507, 1996.

Steiner, J. P., Connolly, M.A., Valentine, H.L., Hamilton, Gregory S., Dawson, T.M., Hester, L. and Snyder, S.H. Neurotrophic actions of nonimmunosuppressive analogues of immunosuppressive drugs FK506, rapamycin and cyclosporin A. Nature Medicine 3:421-428, 1997.

Burnett, P.E., Barrow, R.K., Cohen, N.A., Snyder, S.H. and Sabatini, D.M. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. PNAS 95:1432-1437, 1998.

Sabatini, D.M., Barrow, R.K., Blackshaw, S., Burnett, P.E., Lai, M.M., Field, M.E., Bahr, B.A., Kirsch, J., Betz, H. and Snyder, S.H. Interaction of RAFT1 with the clustering protein gephyrin required for rapamycin-sensitive signaling. Science 284:1161-1164, 1999.

Saiardi A, Bhandari R, Resnick AC, Snowman AM, Snyder SH. Phosphorylation of proteins by inositol pyrophosphates. Science. 2004 Dec 17;306(5704):2101-5.

van Rossum DB, Patterson RL, Sharma S, Barrow RK, Kornberg M, Gill DL, Snyder SH. Phospholipase C1 controls surface expression of TRPC3 through an intermolecular PH domain. Nature 2005 March 3; 434: 99-104.

Bhandari R, Saiardi A, Ahmadibeni Y, Snowman AM, Resnick AC, Kristiansen TZ, Molina H, Pandey A, Werner JK Jr, Juluri KR, Xu Y, Prestwich GD, Parang K, Snyder SH. Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event. Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15305- 10.

Subramaniam S, Sixt KM, Barrow R, Snyder SH. Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity. Science. 2009 Jun 5;324(5932):1327- 30. PMC2745286

Chakraborty A, Koldobskiy MA, Bello NT, Maxwell M, Potter JJ, Juluri KR, Maag D, Kim S, Huang AS, Dailey MJ, Saleh M, Snowman AM, Moran TH, Mezey E, Snyder SH. Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. Cell 2010 Dec 10; 143 (6): 897-

Kim S, Kim SF, Maag D, Maxwell MJ, Resnick AC, Juluri KR, Chakraborty A, Koldobskiy MA, Cha SH, Barrow R, Snowman AM, Snyder SH. Amino acid signaling to mTOR mediated by inositol polyphosphate multikinase. Cell Metab. 2011 Feb 2; 13 (2): 215-224.

Gases and D-Amino Acids as Putative Neurotransmitters:

Discovery that NO mediates glutamate-NMDA transmission via cGMP. Purification, cloning and localizations of neuronal NO synthase (nNOS). Discovery of abnormal aggressive and sexual behavior in nNOS knockout mice. Establishing NO as a neurotransmitter of penile erection and non-adrenergic/non-cholinergic transmission (NANC) in the gut. Discovery of nNOS interacting proteins that regulate NO formation. Localization of neuronal CO forming heme oxygenase 2 (HO2) selectively in cGMP forming areas suggesting synaptic function. Establishing CO as a transmitter of intestinal NANC neurotransmission and penile ejaculation. Elucidating how neuronal depolarization activates HO2 by phosphorylation. Discovery of neuroprotective and cytoprotective roles of bilirubin mediated by a biliverdin reductase cycle affording 10,000-fold amplication of bilirubin actions. Discovery of hydrogen sulfide as a major endothelial derived relaxing factor. Discovery of localization of D-serine to glia and establishing D-serine as endogenous ligand for NMDA receptors. Cloning serine racemase which forms D-serine. Discovery of a cell death signaling cascade whereby apoptotic stimuli activate NO formation to nitrosylate glyceraldehyde-3-phosphate- dehydrogenase which binds to Siah, translocate to the nucleus and leads to selective protein degradation.

Bredt, D.S. and Snyder, S.H. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. PNAS 86:9030-9033, 1989.

Bredt, D.S. and Snyder, S.H. Isolation of nitric oxide synthetase, a calmodulin- requiring enzyme. PNAS 87:682-685, 1990.

Bredt, D.S., Hwang, P.M. and Snyder, S.H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature 347:768-770, 1990.

Bredt, D.S., Hwang, P.M., Glatt, C.E., Lowenstein, C., Reed, R.R. and Snyder, S.H. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P- 450 reductase. Nature 351:714-718, 1991.

Bredt, D.S., Glatt, C.E., Hwang, P.M., Fotuhi, M., Dawson, T.M. and Snyder, S.H. Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of mammalian central nervous system together with NADPH diaphorase. Neuron 7:615-624, 1991.

Verma, A., Hirsch, D.J., Glatt, C.E., Ronnett, G.V. and Snyder, S.H. Carbon monoxide, a putative neural messenger: heme oxygenase localizations and cyclic GMP regulation. Science 259:381-384, 1993.

Dawson, V.L., Dawson, T.M., London, E.D., Bredt, D.S. and Snyder, S.H. Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. PNAS 88:6368-6371, 1991.

Burnett, A.L., Lowenstein, C.J., Bredt, D.S., Chang, T.S. and Snyder, S.H. Nitric oxide: a physiologic mediator of penile erection. Science 257:401-403, 1992.

Huang, P.L., Dawson, T.M., Bredt, D.S., Snyder, S.H. and Fishman, M.C. Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75:1273-1286, 1993.

Schell, M. J., Molliver, M.E. and Snyder, S. H. D-Serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release. PNAS 92:3948-3952, 1995.

Nelson, R.J., Demas, G.E., Huang, P.L., Fishman, M.C., Dawson, V.L., Dawson, T.M. and Snyder, S.H. Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. Nature 378:383-386, 1995.

Zakhary, R., Gaine, S.P., Dinerman, J.L., Ruat, M., Flavahan, N.A., Snyder, S.H. Heme oxygenase 2: Endothelial and neuronal localization and role in endothelium- dependent relaxation. PNAS 93:795-798, 1996.

Schell, M.J., Brady, Jr., R.O., Molliver, M.E. and Snyder, S.H. D-Serine as a neuromodulator: regional and developmental localizations in rat brain glia resemble NMDA receptors. J. Neurosci. 17:1604-1615, 1997.

Jaffrey, S.R., Snowman, A.M., Eliasson, M.J.L., Cohen, N.A. and Snyder, S.H. CAPON: a protein associated with neuronal nitric oxide synthase which regulates its interactions with PSD95. Neuron 20:115-124, 1998.

Wolosker, H., Sheth, K.N., Takahashi, M., Mothet, J.-P., Brady, Jr., R.O., Ferris, C.D. and Snyder, S.H. Purification of serine racemase: biosynthesis of the neuromodulator D-serine. PNAS 96:721-725, 1999.

Wolosker, H., Blackshaw, S. and Snyder, S.H. Serine racemase: A glial enzyme synthesizing D-serine to regulate glutamate-NMDA neurotransmission. PNAS 96:13409-13414, 1999.

Fang, M., Jaffrey, S.R., Sawa, S., Ye, K., Luo, X. and Snyder, S.H. Dexras 1: A G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 28:183-193, 2000.

Jaffrey, S.R., Erdjument-Bromage, H., Ferris, C.D., Tempst, P. and Snyder, S.H. Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nature Cell Biology 3:193-197, 2001.

Baranano, D.E., Rao, M., Ferris, C.D. and Snyder, S.H. Biliverdin reductase: a major physiologic cytoprotectant. PNAS 99:16093-16098, 2002.

Boehning, D., Moon, C., Sharma, S., Hurt, J.K., Hester, L.D., Ronnett, G.V., Shugar, D. and Snyder, S.H. Carbon monoxide neurotransmission activated by CK2 phosphorylation of heme oxygenase-2. Neuron 40:129-137, 2003.

Boehning D, Sedaghat L, Sedlak TW, Snyder SH. Heme oxygenase-2 is activated by calcium-calmodulin. J Biol Chem. 2004 Jul 23;279(30):30927-30

Hara MR, Agrawal N, Kim SF, Cascio MB, Fujimuro M, Ozeki Y, Takahashi M, Cheah JH, Tankou SK, Hester LD, Ferris CD, Hayward SD, Snyder SH, Sawa A. S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation following Siah1 binding. Nat Cell Biol. 2005 Jul;7(7):665-74.

Sen N, Hara MR, Kornberg MD, Cascio MB, Bae BI, Shahani N, Thomas B, Dawson TM, Dawson VL, Snyder SH, Sawa A. Nitric oxide-induced nuclear GAPDH activates p300/CBP and mediates apoptosis. Nat Cell Biol. 2008 Jul;10(7):866-73.

Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, Meng Q, Mustafa AK, Mu W, Zhang S, Snyder SH, Wang R. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science. 2008 Oct 24;322(5901):587-90.

Mustafa AK, Gadalla MM, Sen N, Kim S, Mu W, Gazi S, Barrow RK, Yan G, Wang R and Snyder SH. H2S signals through protein S-sulfhydration. Science Signaling 2009 Nov 10;(2):1-8.

Kornberg MD, Sen N, Hara MR, Juluri KR, Nguyen JV, Snowman AM, Law L, Hester LD, Snyder SH. GAPDH mediates nitrosylation of nuclear proteins. Nat Cell Biol 2010 Nov; 12 (11): 1094-1100.

Ho GP, Selvakumar B, Mukai J, Hester LD, Wang Y, Gogos JA, Snyder SH. Neuron. 2011 Jul 14;71(1):131-41. S-Nitrosylation and S-Palmitoylation Reciprocally Regulate Synaptic Targeting of PSD-95.

Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM, Snyder SH. Cystathionine -lyase deficiency mediates neurodegeneration in Huntington’s disease. Nature 2014 May 1;509(7498):96-100.