activity involves increases in both c-jun mRNA and 
protein. Moreover, gel retardation assays vv^ith oligo- 
mers containing the AP I- and CRE-binding sites 
demonstrate that SP induces specific retardation 
bands consistent with increases in AP I and CRE 
complexes. 
These experiments suggest that SP-mediated stim- 
ulation of cells involves the participation of two sig- 
naling pathways, resulting in the activation of sev- 
eral transcriptional regulatory mechanisms. 
The Role of SP in Immune Responses: 
A Molecular Analysis 
Previous work in Dr. Payan's laboratory, using 
well-defined animal models of inflammation and in 
vitro culture systems with mixed populations of 
lymphocytes, showed that SP amplifies and modu- 
lates certain aspects of the immune and inflamma- 
tion responses. To analyze SP's "immunological 
properties" at the molecular level, the group has 
transfected the rat SPR cDNA into the Jurkat T lym- 
phocyte cell line and has established stable transfec- 
tants. Jurkat-SPR cells demonstrate specific SP bind- 
ing and functional responses to the peptide. Of great 
interest is the fact that in this cell line SP stimulation 
results in enhanced cell growth and the increased 
expression of interleukin-2 receptors and the cell- 
cell recognition molecule CD2. 
Biochemical Characterization 
of Recombinant Rat Agrin 
A full-length cDNA for rat agrin has been tran- 
siently expressed in COS cells and stably expressed 
in the neuronal-like cell line PCI 2. Dr. Payan's 
group is in the process of characterizing the recom- 
binant agrin in terms of its AChR-clustering ability 
and also beginning to examine the biochemical 
properties of the protease-inhibitor domains pres- 
ent at the amino terminus of the molecule. 
Using in situ hybridization with a probe that rec- 
ognizes all agrin isoforms, Dr. Payan and his col- 
leagues have demonstrated that agrin message is 
widely expressed during mammalian embryogene- 
sis. In the developing rat, particularly high levels of 
expression are found in the dorsal root and cranial 
ganglia, gut, whisker rudiments, penis, snout, teeth, 
retina, hippocampus, cerebral cortex, and the lin- 
ing of brain ventricles. Functional analysis of the 
recombinant rat protein shows that it is a potent 
inhibitor of the proteases trypsin, chymotrypsin, 
and plasmin, but not thrombin or the plasminogen 
activators. Dr. Payan and his colleagues conclude 
that agrin may play multiple roles in mammalian 
development, including the regulation of proteoly- 
sis in the extracellular matrix. 
Dr. Payan is also Associate Professor in resi- 
dence in the Departments of Medicine (Infectious 
Disease) and Microbiology and Immunology at 
the University of California, San Francisco. 
Books and Chapters of Books 
Payan, D.G. 1992. Nonsteroidal antiinflammatory 
agents; nonopiate analgesics; drugs used in gout. 
In Basic and Clinical Pharmacology (Katzung, 
B.C., Ed.). Palo Alto, CA: Appleton & Lange, pp 
491-512. 
Payan, D.G. 1992. The role of neuropeptides and 
inflammation. In Inflammation: Basic Princi- 
ples and Clinical Correlates (Gallin, J.I, Gold- 
stein, I.M., and Snyderman, R., Eds.). New York: 
Raven, pp 177-192. 
Articles 
Gilbert, M., and Payan, D.G. 1991- Interactions 
between the nervous and immune systems. Front 
Neuroendocrinol 12:299-322. 
Harrowe, G., Sudduth-Klinger, J., and Payan, 
D.G. 1 992. Measles virus-substance P receptor in- 
teractions: Jurkat lymphocytes transfected with 
the substance P receptor cDNA enhance measles 
virus fusion and replication. Cell Mol Neurobiol 
12:397-409. 
Mitsuhashi, M., Akitaya, T., Turk, C.W., and 
Payan, D.G. 1991. Amyloid ^ protein substituent 
peptides do not interact with the substance P re- 
ceptor expressed in cultured cells. Brain Res Mol 
Brain Res 11:177-180. 
Mitsuhashi, M., Mitsuhashi, T., Dazin, P.F., and 
Payan, D.G. 1991- Agonistic activities of hista- 
mine-albumin conjugates at histamine H2 recep- 
tors on human HL-6O promyelocytic leukemia 
cells. Mol Pharmacol 40:271-215. 
Mitsuhashi, M., Ohashi, Y., Shichijo, S., Chris- 
tian, C, Sudduth-Klinger, J., Harrowe, G., and 
Payan, D.G. 1992. Multiple intracellular signal- 
ing pathways of the neuropeptide substance-P re- 
ceptor . J Neurosci Res 32:437-443. 
Mitsuhashi, M., and Payan, D.G. 1992. Functional 
diversity of histamine and histamine receptors. / 
Invest Dermatol 98:8S-1 IS. 
Shichijo, S., Payan, D.G., Harrowe, G., and Mitsu- 
hashi, M. 1991. Histamine effects on the 5-HTn, 
receptor expressed in Xenopus oocytes. J Neuro- 
sciRes 30:316-320. 
Sudduth-Klinger, J., Schumann, M., Gardner, P., 
and Payan, D.G. 1992. Functional and immuno- 
logical responses of Jurkat lymphocytes trans- 
fected with the substance P receptor. Cell Mol 
Neurobiol 12:379-395. 
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