Biomaterial Database

Pharmacological characterization of muscarinic acetylcholine binding sites in human and bovine cerebral microvessels. 1995

D G Linville, and E Hamel

Laboratory of Cerebrovascular Research, Montreal Neurological Institute, Québec, Canada.

The aim of this study was to investigate the presence of muscarinic receptors in human brain microvessels (MVs) and capillaries (CAPs) and, further, to pharmacologically characterize these receptors as well as those in bovine cerebral microvascular beds. For this purpose, the binding of [3H]N-methyl scopolamine ([3H]NMS) was assessed in isolated human and bovine cerebral MVs and CAPs and competition studies were performed against [3H]NMS binding with several well characterized muscarinic antagonists. The antagonist cerebrovascular affinity constants (pKD) were determined with the computer-fitting software LIGAND and then compared by correlation analyses to their reported affinities (pKi) at the five cloned muscarinic receptors. The specific binding of [3H]NMS to human and bovine MVs and CAPs was saturable, of high affinity and competitively inhibited by muscarinic antagonists. Heterogeneous populations of muscarinic binding sites were found in the microvascular tissues from both species. In human cortical MVs, the pharmacological binding profile obtained from various muscarinic receptor antagonists was best correlated to that of the cloned ml (r = 0.95; p < 0.001) and less so m5 (r = 0.77; p = 0.025) receptor subtypes while in bovine MVs, the presence of the m1 subtype was strongly suggested. Cerebrovascular affinities obtained for selected muscarinic antagonists in single preparations of human and bovine CAPs were suggestive of the presence of M1/m1 and M3/m3 receptor subtypes, and possibly the m5 subtype in bovine CAPs. The detection of M1/m1, M3/m3 and possibly m5 muscarinic receptor subtypes in brain microcirculation is consistent with reports where these receptors have been shown to mediate vasoconstriction, vasodilatation, and activation of nitric oxide synthase, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008833	Microcirculation	The circulation of the BLOOD through the MICROVASCULAR NETWORK.	Microvascular Blood Flow,Microvascular Circulation,Blood Flow, Microvascular,Circulation, Microvascular,Flow, Microvascular Blood,Microvascular Blood Flows,Microvascular Circulations
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D011869	Radioligand Assay	Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).	Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
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
D002196	Capillaries	The minute vessels that connect arterioles and venules.	Capillary Beds,Sinusoidal Beds,Sinusoids,Bed, Sinusoidal,Beds, Sinusoidal,Capillary,Capillary Bed,Sinusoid,Sinusoidal Bed
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
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
D002560	Cerebrovascular Circulation	The circulation of blood through the BLOOD VESSELS of the BRAIN.	Brain Blood Flow,Regional Cerebral Blood Flow,Cerebral Blood Flow,Cerebral Circulation,Cerebral Perfusion Pressure,Circulation, Cerebrovascular,Blood Flow, Brain,Blood Flow, Cerebral,Brain Blood Flows,Cerebral Blood Flows,Cerebral Circulations,Cerebral Perfusion Pressures,Circulation, Cerebral,Flow, Brain Blood,Flow, Cerebral Blood,Perfusion Pressure, Cerebral,Pressure, Cerebral Perfusion