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Adenosine A1-receptor coupling to phosphoinositide metabolism in pregnant guinea pig myometrium.
- Source :
-
The American journal of physiology [Am J Physiol] 1991 Nov; Vol. 261 (5 Pt 1), pp. E665-72. - Publication Year :
- 1991
-
Abstract
- Adenosine contracts pregnant and nonpregnant guinea pig myometrial smooth muscle (MSM). We have 1) described dissociation of A1-adenosine receptors from adenylate cyclase inhibition in nonpregnant MSM (M. A. Smith, J. L. Silverstein, D. P. Westfall, and I. L. O. Buxton, Cell. Signal. 1: 357-365, 1989); 2) described appearance of such inhibitory coupling in pregnant MSM [W. P. Schiemann, D. P. Westfall, and I. L. O. Buxton, Am. J. Physiol. 261 (Endocrinol. Metab. 24): E141-E150, 1991]; and 3) demonstrated a role for myometrial A1 receptors in the rapid formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in nonpregnant MSM and the cyclooxygenase dependence of this effect (W. P. Schiemann, K. O. Doggwiller, and I. L. O. Buxton. J. Pharmacol. Exp. Ther. 258: 429-437, 1991). To further characterize adenosine action in pregnant tissue, we explored A1 coupling to increased phosphoinositide hydrolysis in near-term pregnant MSM. The A1-receptor agonist (+)-N6-(2-phenylisopropyl)adenosine stimulates the rapid dose-dependent formation of Ins(1,4,5)P3 and stimulates rapid degradation of uterine inositol monophosphates (InsP) in a manner paralleling increases in inositol polyphosphates. Both A1-mediated responses were blocked by the A1 antagonist 8-(p-sulfophenyl)theophylline, and, unlike the effect observed in nonpregnant MSM, treatment of pregnant MSM with either meclofenamate or indomethacin failed to block A1-mediated increases in Ins(1,4,5)P3. Pretreatment of MSM with either Li+ or pertussis toxin failed to alter either Ins(1,4,5)P3 formation or InsP degradation. Furthermore, assay of inositol phosphomonoesterase (InsPase) activity in the presence or absence of Li+ confirmed the existence of an MSM Li(+)-insensitive InsPase enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
- Subjects :
- Animals
Chromatography, High Pressure Liquid
Female
Guinea Pigs
Hydrolysis drug effects
Inositol 1,4,5-Trisphosphate metabolism
Inositol Phosphates metabolism
Lithium pharmacology
Muscle, Smooth metabolism
Phenylisopropyladenosine pharmacology
Pregnancy
Myometrium metabolism
Phosphatidylinositols metabolism
Pregnancy, Animal metabolism
Receptors, Purinergic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9513
- Volume :
- 261
- Issue :
- 5 Pt 1
- Database :
- MEDLINE
- Journal :
- The American journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 1659216
- Full Text :
- https://doi.org/10.1152/ajpendo.1991.261.5.E665