This application outlines a study on intrinsic neuroregulatory mechanisms of cells which produce endogenous opiate and related peptides. The major hypothesis to be tested is that specific inhibitory and stimulatory mechanisms exist which regulate secretion of opiomelanocortin peptides. To examine the hypothesis of whether inhibition or stimulation of peptide secretion occurs directly on opiomelanocortin cells, specific neurotransmitters and neurotoxins, narcotic antagonist drugs, and selected opiate or hypothalamic peptides will be used in rodent pituitary glands in vitro. Since inhibition or stimulation of peptide secretion may also be affected by central nervous system mechanisms, an intact in vivo rodent animal model, will be treated with the same neurotoxins or narcotic antagonists as the in vitro studies. To measure the level of output of peptides from either the in vitro or in vivo systems, bioassay or radioimmunoassay for melanocyte-stimulating hormone, or radioimmunoassay for beta-endorphin, will be used. Specific effects of neurotoxins in vivo will be confirmed by high pressure liquid chromatographic (HPLC) analysis of pituitary and brain neurotransmitters. Radioimmunoassay for pituitary tissue levels of beta-endorphin will be performed in order to compare stored levels of peptide with released material in serum. Finally, cytologic and immunohistochemical studies of opiomelanocortin cells, using qualitative and quantitative methods for evaluation, will be performed within the same experimental groups as those assayed for peptides, to determine how individual groups of pituitary secretory cells respond to inhibition or stimulation. It is anticipated that neurotoxic agents or opiate antagonist drugs may have direct effects on stimulation or prevention of pituitary peptide secretion, depending upon the agents' selectivity for a particular neurotransmitter. The use of in vitro and in vivo studies on the rodent pituitary gland model, will provide support for specific mechanisms which affect release and storage of endogenous opiate molecules.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021256-02
Application #
3402213
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of New Mexico
Department
Type
Schools of Medicine
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Saland, L C; Perrone-Bizzozero, N I; Sower, A et al. (1996) Alterations in GAP-43-immunoreactive innervation in the aging rat pituitary. Neurosci Lett 208:138-42
Saland, L C; Samora, A; Apodaca, A et al. (1995) Regulation of pituitary beta-endorphin secretion in aging rats: in vitro responsiveness to dopamine. Life Sci 56:1415-25
Saland, L C; Samora, A; Sanchez, P et al. (1993) Immunocytochemical studies of tryptophan hydroxylase, tyrosine hydroxylase, and serotonin innervation in the aging rat neurointermediate pituitary. Exp Neurol 121:119-26
Carr, J A; Saland, L C; Samora, A et al. (1993) Effects of the enkephalin analog (D-Met2,Pro5)-enkephalinamide on alpha-melanocyte-stimulating hormone secretion. Regul Pept 47:141-50
Saland, L C; Carr, J A; Samora, A et al. (1992) Benzodiazepine suppression of corticotropin-releasing factor (CRF)-induced beta-endorphin release from rat neurointermediate pituitary. Peptides 13:913-7
Carr, J A; Norris, D O; Samora, A (1991) Organization of tyrosine hydroxylase-immunoreactive neurons in the di- and mesencephalon of the American bullfrog (Rana catesbeiana) during metamorphosis. Cell Tissue Res 263:155-63
Carr, J A; Saland, L C; Samora, A et al. (1991) In vivo effects of serotonergic agents on alpha-melanocyte-stimulating hormone secretion. Neuroendocrinology 54:616-22
Saland, L C; Carr, J A; Samora, A et al. (1991) Interaction of corticotropin-releasing factor (CRF) and alpha-helical CRF on rat neurointermediate lobes: in vitro studies. Neuropeptides 19:213-21
Saland, L C; Samora, A; Desai, S (1990) Ultrastructure of the pituitary intermediate lobe in aging rats. Anat Rec 227:97-103
Saland, L C; Reyes, E; Samora, A et al. (1990) Chronic naltrexone infusion: effects on innervation of rat neurointermediate lobe. Brain Res Bull 24:779-86

Showing the most recent 10 out of 14 publications