Antagonism of progesterone receptor suppresses carotid body responses to hypoxia and nicotine in rat pups.
Summary of "Antagonism of progesterone receptor suppresses carotid body responses to hypoxia and nicotine in rat pups."
We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 μg/g/d) or vehicle between postnatal days 3 and 15. In 11-14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in vitro, 10% O2 in vivo) and to nicotinic receptor agonists (as an excitatory modulator of carotid body activity-nicotine 100 μM for in vitro studies, and epibatidine 5 μg/kg, i.p., which mainly acts on peripheral nicotinic receptors, for in vivo studies). The carotid body responses to hypoxia and nicotine were drastically reduced by mifepristone. Compared with vehicle, mifepristone-treated rats had a reduced body weight. The ventilatory response to epibatidine was attenuated; however, the hypoxic ventilatory response was similar between vehicle and mifepristone-treated pups. Immunohistochemical staining revealed that mifepristone treatment did not change carotid body morphology. We conclude that PR activity is a critical factor ensuring proper carotid body function in newborn rats.
Affiliation
Department of Pediatrics, Laval University, Centre de Recherche (D0-711), Hôpital St.-François d'Assise, 10 rue de l'Espinay, QC, G1L 3L5, Canada.
Journal Details
This article was published in the following journal.
Name: Neuroscience
ISSN: 1873-7544
Pages: 103-9
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22326965
- DOI: http://dx.doi.org/10.1016/j.neuroscience.2012.01.041
Medical and Biotech [MESH] Definitions
Carotid Body
A small cluster of chemoreceptive and supporting cells located near the bifurcation of the internal carotid artery. The carotid body, which is richly supplied with fenestrated capillaries, senses the pH, carbon dioxide, and oxygen concentrations in the blood and plays a crucial role in their homeostatic control.
Receptors, Progesterone
Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.
Carotid Artery Injuries
Damages to the CAROTID ARTERIES caused either by blunt force or penetrating trauma, such as CRANIOCEREBRAL TRAUMA; THORACIC INJURIES; and NECK INJURIES. Damaged carotid arteries can lead to CAROTID ARTERY THROMBOSIS; CAROTID-CAVERNOUS SINUS FISTULA; pseudoaneurysm formation; and INTERNAL CAROTID ARTERY DISSECTION. (From Am J Forensic Med Pathol 1997, 18:251; J Trauma 1994, 37:473)
Carotid Artery Diseases
Pathological conditions involving the CAROTID ARTERIES, including the common, internal, and external carotid arteries. ATHEROSCLEROSIS and TRAUMA are relatively frequent causes of carotid artery pathology.
Hypoxia-inducible Factor 1
A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.
PubMed Articles
The progesterone receptor is able to bind to a large number and variety of ligands that elicit a broad range of transcriptional responses ranging from full agonism to full antagonism and numerous mixe...
Immunosensory signalling by carotid body chemoreceptors.
Injections of lipopolysaccharide (LPS) have been used to produce the signs of sepsis and study their underlying mechanisms. Intravenous (IV) injections of LPS in anesthetized cats induce tachypnea, ta...
Intermittent hypoxia augments acute hypoxic sensing via HIF-mediated ROS.
Carotid bodies and neonatal adrenal medullary chromaffin cells (AMC) respond rapidly to acute hypoxia before compromising cellular functions. Responses to acute hypoxia are dynamically altered by chro...
Spermine attenuates carotid body glomus cell oxygen sensing by inhibiting L-type Ca²(+) channels.
An increase in intracellular Ca²(+) is crucial to O₂ sensing by the carotid body. Polyamines have been reported to modulate both the extracellular Ca²(+)-sensing receptor (CaR) and voltage-gated C...
Phrenic long-term facilitation (pLTF) is a form of respiratory plasticity induced by acute intermittent hypoxia (AIH) or episodic carotid chemoafferent neuron activation. Surprisingly, residual pLTF i...
Clinical Trials
Progesterone for the Treatment of Cocaine Dependence - 1
Past research has demonstrated that cocaine dependent women experience less severe responses to cocaine during the luteal phase of the menstrual cycle, when estrogen and progesterone conce...
Bradykinin Receptor Antagonism During Cardiopulmonary Bypass- Specific Aim 3
Each year over a million patients worldwide undergo cardiac surgery requiring cardiopulmonary bypass (CPB). CPB is associated with significant morbidity including the transfusion of alloge...
Letrozole in Women With Advanced Estrogen/Progesterone Receptor Positive Uterine Leiomyosarcoma
The purpose of this research study is to determine if letrozole is effective at controlling the growth or spread of estrogen and/or progesterone receptor positive uterine leiomyosarcoma....
RATIONALE: Studying samples of blood in the laboratory from patients with cancer receiving anastrozole may help doctors learn more about changes that occur in DNA and identify biomarkers r...
Evaluating the Roles of Estrogen and Progesterone in Heart Metabolism
Estrogen and progesterone are two main female sex hormones. When a woman goes through menopause, the body's production of estrogen and progesterone significantly decreases. Recent studies...
