Biomaterial Database

Allosteric interactions between muscarinic agonist binding sites and effector sites demonstrated by the use of bisquaternary pyridinium oximes. 1985

Y Kloog, and M Sokolovsky

Agonist binding to muscarinic receptors from rat brain stem and cerebral cortex was studied using bisquaternary pyridinium oximes for detecting possible interactions between agonist binding sites and sites of the effector guanosine 5' (beta, gamma-imino) triphosphate (Gpp(NH)p) and Co2+. Pretreatment of either brain stem or cortical homogenates with 200 microM 1-(2-hydroxyiminoethylpyridinium) 1-(3-phenylcarboxypyridinium) dimethylether (HGG-12) reduced the affinity of muscarinic agonists. No change was observed in the relative proportions of high (RH) and low (RL) affinity agonist binding sites. However, the oxime affected the processes of interconversion between these sites. Thus, unlike in control membranes, HGG-12 treated brain stem membranes, Gpp(NH)p could not induce conversion of RH to RL, and in cortical membranes Co2+ could not induce conversion of RL to RH. These results suggest that HGG-12 inactivates a component which is involved in both processes of induced-interconversion. Induced-interconversion between RH and RL was not affected in membranes treated with HGG-12 in the presence of carbamylcholine in concentrations at which mainly RH is occupied by the agonist. The occupation of RH by carbamylcholine protected both RH and RL from the effects of the oxime. The possible role of the molecular events involved is discussed.

UI	MeSH Term	Description	Entries
D010091	Oximes	Compounds that contain the radical R2C	Aldoximes,Hydroxyimino Compounds,Ketoxime,Ketoximes,Oxime,Compounds, Hydroxyimino
D010095	Oxotremorine	A non-hydrolyzed muscarinic agonist used as a research tool.	Oxytremorine
D010277	Parasympathomimetics	Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here.	Parasympathomimetic Agents,Parasympathomimetic Drugs,Parasympathomimetic Effect,Parasympathomimetic Effects,Agents, Parasympathomimetic,Drugs, Parasympathomimetic,Effect, Parasympathomimetic,Effects, Parasympathomimetic
D011726	Pyridinium Compounds	Derivatives of PYRIDINE containing a cation C5H5NH or radical C5H6N.	Compounds, Pyridinium
D011976	Receptors, Muscarinic	One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.	Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
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
D002217	Carbachol	A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.	Carbamylcholine,Carbacholine,Carbamann,Carbamoylcholine,Carbastat,Carbocholine,Carboptic,Doryl,Isopto Carbachol,Jestryl,Miostat,Carbachol, Isopto
D002540	Cerebral Cortex	The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.	Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003035	Cobalt	A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.	Cobalt-59,Cobalt 59
D006165	Guanylyl Imidodiphosphate	A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of ADENYLYL CYCLASES.	GMP-PNP,GMP-P(NH)P,Gpp(NH)p,Guanosine 5'-(Beta,Gamma-Imido)Triphosphate,Guanyl-5'-Imidodiphosphate,P(NH)PPG,Guanyl 5' Imidodiphosphate,Imidodiphosphate, Guanylyl