IONIC MECHANISMS RELATED TO SECRETION IN PITUITARY CELLS

  • Oxford, Gerry, (PI)

Project: Research project

Description

The functional coupling between membrane electrical events and exocytotic
release of hormones from endocrine cells is a key element in the
physiology of secretion in endocrine glands. In the case of pituitary
hormone secretion the membrane ion channels involved and the molecular
mechanisms coupling stimulatory and inhibitory secretogogue receptors to
these ion channels are only now being revealed. This task is complicated
due to the presence of cellular subtypes secreting more than one hormone
and interactions between more than one regulator of secretion. Many of
the key secretagogue receptors belong to the superfamily of seven
membrane spanning domain receptors that transduce ligand binding into
cellular action via guanine nucleotide binding proteins (G-proteins).
Among such receptors are those for dopamine (D2 type), the primary
regulator of prolactin secretion, and somatostatin which governs
inhibition of growth hormone release. The principle objective of this
study is to employ patch clamp electrophysiological methods to examine
the changes in ion channel function which underlie the actions of these
and other agonists on individual pituitary cells in culture, and to
elucidate the coupling mechanisms, both common and unique, which regulate
excitation-secretion coupling in secretory subtypes. Normal rat anterior
pituitary cells will be identified using the reverse hemolytic plaque
assay (RHPA) and a newly developed method, the sequential cell immunoblot
assay (SCIBA) to unambiguously discriminate cell types and quantify
changes in secretion at the single cell level. In addition we will
examine cell lines in which normal and mutated dopamine receptors are
recombined with other elements of the signal transduction pathway. Key
issues to be addressed are (1) the identity of G-proteins coupling D2
receptors to ion channels, (2) the mechanisms involved in this coupling,
(3) the structural determinants of coupling specificity of receptors and
G-proteins, (4) the nature of the relative immunity of D2 receptors to
desensitization, and (5) the precise role of ion channel and ion
concentration changes in the regulation of hormone secretion. This
research will lead to a clearer understanding of the events underlying
regulated hormone secretion in pituitary cells. In addition, the common
identity of dopamine receptor subtypes in both pituitary and brain
suggest that these studies may provide mechanistic insight into the
actions of these neurotransmitters in affective disorders and neural
regulation of vegetative functions.
StatusFinished
Effective start/end date7/1/826/30/05

Funding

  • National Institutes of Health
  • National Institutes of Health: $225,948.00
  • National Institutes of Health
  • National Institutes of Health: $228,876.00
  • National Institutes of Health
  • National Institutes of Health: $207,870.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $235,742.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $242,813.00
  • National Institutes of Health: $185,281.00
  • National Institutes of Health: $179,058.00
  • National Institutes of Health: $199,088.00
  • National Institutes of Health: $36,691.00
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Ion Channels
Guanine Nucleotides
Hormones
Carrier Proteins
Dopamine Receptors
Neurotransmitter Agents
Endocrine Cells
Endocrine Glands
Membranes
Potassium Channels
Patch-Clamp Techniques
Dopamine D2 Receptors
Somatostatin
Pituitary Hormones
Mood Disorders
Prolactin
Inwardly Rectifying Potassium Channel
Growth Hormone
Signal Transduction
Cell Culture Techniques

Keywords

  • Medicine(all)
  • Neuroscience(all)