UTERINE OXYTOCIN RECEPTORS AND ION CHANNELS

Project: Research project

Description

Oxytocin, the peptide hormone produced in the hypothalamus, increases the
contractility of its physiological target tissues, the uterine smooth
muscle and myoepithelial cells of the breast. The molecular mechanism by
which oxytocin exerts its effect is still unknown, mainly because of the
great experimental difficulty of studying these tissues. A promising
alternative for such studies appears to be the Xenopus oocyte. Preliminary
experiments have shown that oocytes acquire oxytocin sensitivity when
injected with a mRNA preparation derived from estrogen-primed uterine
smooth muscle. Estrogen treatment is known to induce the same changes in
the myometrium as occuring in preparation for parturition: upregulation of
oxytocin receptors, gap junctions, and of Alpha-adrenergic receptors. In
parallel to acquisition of oxytocin sensitivity, pairs of mRNA-injected
oocytes also develop gap junctions. The ocytocin response in mRNA-injected oocytes consists of a
dose-dependent, sustained and reversible depolarization of the cell
membrane. This hormone-induced change in membrane potential indicates that
oxytocin receptors are incorporated into the oocyte membrane and are either
linked to ion channels or are ion channels on their own. Xenopus oocytes
are readily amenable to electrophysiological studies and it is proposed to
use the mRNA induction of oxytocin sensitivity in these cells to identify
the charge carrying ion species and test criteria for second messengers.
The studies will be started with whole cell voltage clamp techniques to
characterize the oxytocin response at the macroscopic level. Subsequently
patch clamp methods will be employed to continue the investigation at the
single channel level.
StatusFinished
Effective start/end date4/1/863/31/89

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

Oxytocin Receptors
Oxytocin
Ion Channels
Oocytes
Messenger RNA
Gap Junctions
Xenopus
Estrogens
Receptors, Adrenergic, alpha
Peptide Hormones
Myometrium
Second Messenger Systems
Patch-Clamp Techniques
Membrane Potentials
Hypothalamus
Breast
Up-Regulation
Parturition
Hormones
Ions

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)