Biomaterial Database

Differential modulation of muscarinic receptors in the rat brain by repeated exposure to methyl parathion. 2003

Tingting Sun, and Tangeng Ma, and Ing K Ho

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.

The neurochemical and behavioral effects of repeated subdermal administration of methyl parathion (MP) at low doses were investigated. Adult male rats were treated repeatedly with either vehicle or MP subcutaneously (3 mg/kg/day) and observed for the signs of toxicity during the treatment period. The toxic sign, tremor, reached maximum right after 9th injection in MP-treated rats, and declined thereafter. Animals were sacrificed and brains were taken 1 week or 3 weeks after the daily treatment for measurement of acetylcholinesterase (AChE) activity and binding of radioligands, [3H]QNB (nonselective), [3H]pirenzepine (M1-selective), and [3H]AF-DX384 (M2-selective) to muscarinic receptors. With this treatment regimen, the AChE activity in the blood dropped quickly and maintained at 30% of the control level after 6 injections. After 3 weeks of treatment, MP caused 80-90% AChE inhibition and substantial reductions in [3H]QNB binding (9-33%), [3H]pirenzepine binding (9-22%) and [3H]AF-DX384 binding (6-38%) in different brain regions, including striatum, hippocampus, frontal cortex, thalamus and midbrain. After 1 week of treatment, the inhibition of AChE in brain regions was from 54 to 74%, whereas receptor densities were only marginally affected in a few regions. The timing of the changes in receptor population correlates well with the changes in behaviors during the repeated MP exposure. Our findings suggest that down-regulation of muscarinic receptors plays a role in the development of tolerance to MP. And, the regulations of muscarinic receptors were different among receptor subtypes and brain regions.

UI	MeSH Term	Description	Entries
D007279	Injections, Subcutaneous	Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.	Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297	Male		Males
D008743	Methyl Parathion	The methyl homolog of parathion. An effective, but highly toxic, organothiophosphate insecticide and cholinesterase inhibitor.	Metaphos,Parathion Methyl,Dalf,Metacid 50,Methylparathion,Vofatox,Wofatox
D010890	Pirenzepine	An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.	Gastrotsepin,Gastrozepin,L-S 519,LS-519,Piren-Basan,Pirenzepin,Pirenzepin Von Ct,Pirenzepin-Ratiopharm,Pirenzepine Dihydrochloride,Pyrenzepine,Ulcoprotect,Ulgescum,Dihydrochloride, Pirenzepine,LS 519,LS519,Piren Basan,Pirenzepin Ratiopharm,Von Ct, Pirenzepin
D011813	Quinuclidinyl Benzilate	A high-affinity muscarinic antagonist commonly used as a tool in animal and tissue studies.	Benzilate, Quinuclidinyl
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002800	Cholinesterase Inhibitors	Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.	Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D006651	Histocytochemistry	Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods.	Cytochemistry
D000110	Acetylcholinesterase	An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7.	Acetylcholine Hydrolase,Acetylthiocholinesterase,Hydrolase, Acetylcholine
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