Biomaterial Database

Tyrosine kinase inhibitors modulate the ventilatory response to hypoxia in the conscious rat. 1999

M A Czapla, and N Simakajornboon, and G A Holt, and D Gozal

Department of Pediatrics, Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.

Tyrosine kinases (TKs) exert multiple regulatory roles in neuronal activity and synaptic plasticity and could be involved in modulation of cardiovascular and respiratory control mechanisms within the dorsocaudal brain stem. To study this issue, the cardioventilatory responses to 1-microl microinjection within the dorsocaudal brain stem of either vehicle (Veh), the inactive TK inhibitor analog tyrphostin A1 (A1; 1 mM), or the active TK inhibitors genistein (Gen; 10 mM) and tyrphostin A25 (A25; 1 mM) were assessed by whole body plethysmography in unrestrained Sprague-Dawley adult rats. No changes in minute ventilation, heart rate, or mean arterial pressure occurred with Veh, A1, Gen, or A25 during room air breathing (P not significant). However, Gen and A25 attenuated the peak hypoxic ventilatory responses (HVR) to 10% O(2) (P < 0.006 vs. Veh), whereas A1 did not modify HVR (P not significant). HVR reductions by Gen and A25 were primarily due to diminished respiratory frequency enhancements (P < 0.002). No changes in heart rate or mean arterial pressure responses occurred during hypoxia with TK inhibition. In addition, increases in tyrosine phosphorylation of the NR2A/B subunits, but not of the NR2C subunit, of the N-methyl-D-aspartate receptor occurred at 5, 30, and 60 min of hypoxia in the dorsocaudal brain stem and returned to baseline values at 120 min. We conclude that hypoxia induces tyrosine phosphorylation of the N-methyl-D-aspartate glutamate receptor, and TK inhibition within the dorsocaudal brain stem attenuates components of HVR in conscious rats.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D011505	Protein-Tyrosine Kinases	Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.	Tyrosine Protein Kinase,Tyrosine-Specific Protein Kinase,Protein-Tyrosine Kinase,Tyrosine Kinase,Tyrosine Protein Kinases,Tyrosine-Specific Protein Kinases,Tyrosylprotein Kinase,Kinase, Protein-Tyrosine,Kinase, Tyrosine,Kinase, Tyrosine Protein,Kinase, Tyrosine-Specific Protein,Kinase, Tyrosylprotein,Kinases, Protein-Tyrosine,Kinases, Tyrosine Protein,Kinases, Tyrosine-Specific Protein,Protein Kinase, Tyrosine-Specific,Protein Kinases, Tyrosine,Protein Kinases, Tyrosine-Specific,Protein Tyrosine Kinase,Protein Tyrosine Kinases,Tyrosine Specific Protein Kinase,Tyrosine Specific Protein Kinases
D012119	Respiration	The act of breathing with the LUNGS, consisting of INHALATION, or the taking into the lungs of the ambient air, and of EXHALATION, or the expelling of the modified air which contains more CARBON DIOXIDE than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (	Breathing
D001933	Brain Stem	The part of the brain that connects the CEREBRAL HEMISPHERES with the SPINAL CORD. It consists of the MESENCEPHALON; PONS; and MEDULLA OBLONGATA.	Brainstem,Truncus Cerebri,Brain Stems,Brainstems,Cerebri, Truncus,Cerebrus, Truncus,Truncus Cerebrus
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000860	Hypoxia	Sub-optimal OXYGEN levels in the ambient air of living organisms.	Anoxia,Oxygen Deficiency,Anoxemia,Deficiency, Oxygen,Hypoxemia,Deficiencies, Oxygen,Oxygen Deficiencies
D016194	Receptors, N-Methyl-D-Aspartate	A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.	N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus