# ROLE OF ADENYL PURINES IN MYOMETRIAL FUNCTION

> **NIH NIH R01** · UNIVERSITY OF NEVADA RENO · 1993 · $168,173

## Abstract

This project proposes that adenyl purines, compounds known to cause
contraction of uterus, participate in the regulation of human
parturition. The specific aims of this research are to discover the
origins, binding sites and molecular signaling events that subserve the
contractile action of adenyl purines in uterine smooth muscle. The
working hypothesis is that adenyl purines, both adenosine and ATP from
one or more sources stimulate purinergic receptors in myometrial smooth
muscle leading to uterine contraction. We propose that adenyl purines
participate in, or initiate labor and as such, may provide a focal point
for understanding preterm labor in humans. Studies will be conducted with
tissues and freshly isolated cells from both pregnant guinea pigs and
humans. The research plan will be separated into three areas of
investigation. (1) We will determine the origins of adenyl purines in the
uterus. HPLC and radiolabeling studies will investigate the role of
putative purinergic nerves as well as the co-release of purines from
adrenergic and cholinergic nerves in myometrium. Paracrine release of
purines from the smooth muscle of myometrium itself, or from endometrium
will also be tested. (2) The receptor targets for adenyl purines will be
investigated with radioligand binding studies in cells and tissues and
will determine the presence and distribution of purinergic receptors of
the P1 and P2 subtype in circular and longitudinal smooth muscles. These
methods will also be used to determine the nature of regulation of
receptor affinity for agonist and the role of coupling proteins such as
GTP-binding proteins in the molecular action of these receptors.(3)
Pharmacological studies will characterize the actions of adenyl purines
in pregnant uterus. Mechanical contraction of tissues,
electrophysiological measurements of cellular ionic currents and
biochemical measurements of receptor action will be made. Biochemical and
electrophysiological studies will employ tissue segments and purified
smooth muscle cells and will concentrate on the role of purines in the
regulation of cellular Ca+2. Biochemical studies will include measurement
of inositol phosphates, arachidonic acid release, cyclic nucleotide
metabolism and the action of protein kinases. Cellular imaging using
fluorescent pH dyes will be used to determine the regulation of
phospholipase A2 through stimulation of N+/H+ exchange. Intracellular
calcium fluctuations will be studied in cells and tissues using
intracellular fluorescent dyes.

## Key facts

- **NIH application ID:** 2199877
- **Project number:** 5R01HD026227-05
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **SAM.gov UEI:** WLDGTNCFFJZ3
- **Principal Investigator:** IAIN L BUXTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $168,173
- **Award type:** 5
- **Project period:** 1989-09-01 → 1994-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199877

## Citation

> US National Institutes of Health, RePORTER application 2199877, ROLE OF ADENYL PURINES IN MYOMETRIAL FUNCTION (5R01HD026227-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199877. Licensed CC0.

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