We will study synthesis and release of the hormone arginine vasopressin. Steady-state vasopressin mRNA levels will be measured by in situ hybridization techniques using sensitive and specific cDNA probes. Vasopressin release will be monitored by measuring the peptide by radioimmunoassay in culture medium. The first set of studies will focus on vasopressin mRNA dynamics in the suprachiasmatic nuclei (SCN), the site of a known circadian pacemaker. This will be investigated by (i) more precisely defining the time course of our newly discovered vasopressin mRNA rhythm in SCN, (ii) examining the hormonal specificity of this rhythm, and (iii) delineating the developmental onset of the mRNA rhythm. The second set of studies will focus on vasopressin release from SCN. This will be investigated by (i) further developing and validating our perifusion system for studying rhythmic vasopressin release from SCN explants in culture; (ii) examining the specificity of the release rhythm from SCN; and (iii) studying the role of membrane excitability in rhythmic vasopressin release. The third set of studies will focus on (i) probing the relationship between these endogenous rhythms of vasopressin synthesis (mRNA) and release, and (ii) using vasopressin release as a means to study actual circadian clock mechanisms. The results of these studies will provide new insights into mechanisms underlying synthesis and release of peptide hormones.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038116-02
Application #
3237323
Study Section
Endocrinology Study Section (END)
Project Start
1987-01-01
Project End
1989-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Nadakavukaren, J J; Welsh, D K; Reppert, S M (1990) Aluminum fluoride reveals a phosphoinositide system within the suprachiasmatic region of rat hypothalamus. Brain Res 507:181-8
Carlson, L L; Weaver, D R; Reppert, S M (1989) Melatonin signal transduction in hamster brain: inhibition of adenylyl cyclase by a pertussis toxin-sensitive G protein. Endocrinology 125:2670-6
Rivkees, S A; Cassone, V M; Weaver, D R et al. (1989) Melatonin receptors in chick brain: characterization and localization. Endocrinology 125:363-8
Rivkees, S A; Carlson, L L; Reppert, S M (1989) Guanine nucleotide-binding protein regulation of melatonin receptors in lizard brain. Proc Natl Acad Sci U S A 86:3882-6
Rivkees, S A; Chaar, M R; Hanley, D F et al. (1989) Localization and regulation of vasopressin mRNA in human neurons. Synapse 3:246-54
Reppert, S M; Uhl, G R (1988) The vasopressin gene is expressed prior to regulation in the supraoptic nuclei of fetal rats. Brain Res 456:392-6
Gillette, M U; Reppert, S M (1987) The hypothalamic suprachiasmatic nuclei: circadian patterns of vasopressin secretion and neuronal activity in vitro. Brain Res Bull 19:135-9
Reppert, S M; Uhl, G R (1987) Vasopressin messenger ribonucleic acid in supraoptic and suprachiasmatic nuclei: appearance and circadian regulation during development. Endocrinology 120:2483-7