Neuroendocrine action of adrenomedullin and PAMP
| Project/Area Number | 09671034 |
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
TAKANO Koji Branch Hospital, University of Tokyo, School of Medicine,, 医学部・附属病院分院, 助手 (20236243)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Project Status |
Completed(Fiscal Year 1998)
|
| Budget Amount *help |
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥1,900,000 (Direct Cost : ¥1,900,000)
|
|---|
| Keywords | ADRENOMEDULLIN / ADRENOCORTICOTROPIN / CATECHOLAMINE / PAMP / PROLACTIN / HYPERTENSION / 神経機能 |
|---|
| Research Abstract |
The neuroendocrine action and neuronal action of adrenomedullin and PAMP was investigated in human pituitary adenoma cells and rat neuronal cell lines. 1. Adrenomedullin(AM) stimulated prolactin release from human prolactin-secreting pituitary adenoma cells dose-dependently by depolarizing the membrane of these cells through the activation of a nonselective cation current. The activation was mediated through Gs and PKA.It is known that intravenous administration of AM stimulates prolactin secretion in normal human subjects. Our data suggest that the stimulation be due to the direct action of AM on prolactin-secreting cells. This study showed the ionic mechanism of AM action for the first time. 2. PAMP inhibited ACTH secretion from human ACTH-secreting pituitary adenoma cells dose-dependently by hyperpolarizing the membrane of these cells. Under the voltage clamp, PAMP induced an outward current accompanied by an increase of the membrane conductance. The PAMP-induced current showed dist
… More
inct inward rectification and the reversal potential was close to the equilibrium potential of potassium. When the potassium concentration of the extracellular solution was changed, the reversal potential of the PAMP-induced current shifted according to the calculated equilibrium potential of potassium, indicating that PAMP induced an inwardly rectifying potassium current. The hyperpolarization may inhibit action potentials and thus decrease Ca^<2+> influx through the voltage-gated Ca^<2+> channels. 3. The mechanism of action of PAMP on neuronal cells were investigated in NGF-differentiated PCl2 cells. PAMP induced hyperpolarization through the activation of an inwardly rectifying potassium channel. Microinjection of non-hydrolyzable GDP analogue (GDPbetaS) or pretreatment of the cells with pertussis toxin abolished the activation. These indicate that the activation was mediated through a pertussis toxin-sensitive G protein. The subtype of the G protein involved in the signal transduction was investigated using specific antibody against the carboxyl terminal amino acid sequences of Gialpha proteins, which revealed that it was mediated through Gi3. Less
|
Report
(3results)
Research Products
(13results)
