The long-term objective is to understand the role of the neuropeptide vasopressin (VP) as a neurotransmitter or neuromodulator in the mature and developing central nervous system (CNS).
The specific aims are 1) to define the pharmacologic characteristics of brain VP receptors and the post-receptor events involved VP's CNS effects; 2) to determine whether changes in number and affinity of VP receptors in brain and peripheral tissues of Brattleboro rats which lack vasopressin influence cellular responsiveness to the peptide, and whether VP treatment can reverse any changes observed; 3) to determine whether VP binding sites which are expressed in certain brain regions during the early post-natal period in the rat are similar to those which are present in other areas of the adult rat brain, and whether exposure to high levels of vasopressin during the developmental period can alter CNS VP receptor characteristics long-term, and 4) to ascertain whether vasopressin and/or messenger RNA for vasopressin is expressed by neurons which project to brain regions in which developmental VP binding sites are present. To accomplish these goals, a combination of membrane binding techniques and in vitro receptor autoradiography with computer-assisted image analysis will be used. Post-receptor events in vasopressin effects will be measured using tritiated inositol to monitor the hydrolysis of phosphatidylinositol in brain tissue slices and cultured hepatocytes. Vasopressin will be measured in microdissected brain tissue by radioimmunoassay, and will be immunostained in brain neurons using the peroxidase-antiperoxidase technique. Messenger RNA for vasopressin will be localized by in situ hybridization using a radiolabeled oligonucleotide probe and measured by quantitative autoradiography. The ultimate goal is to understand the pharmacologic, developmental, and pathologic characteristics of brain vasopressin receptors. Vasopressinergic function may be impaired in neuropsychiatric disorders such as Alzheimer's disease. Vasopressin treatment has been reported to enhance memory in animals and man. The information obtained in these studies is essential to the development of clinically useful vasopressin analogs with CNS activity.
Showing the most recent 10 out of 100 publications
