Biomaterial Database

Muscarinic receptor stimulation increases the spontaneous [3H]GABA release in the rat substantia nigra through muscarinic receptors localized on striatonigral terminals. 1994

N Kayadjanian, and H Gioanni, and A Ménetrey, and M J Besson

Laboratoire de Neurochimie-Anatomie, Institut des Neurosciences, CNRS URA 1488, Université Pierre, Paris, France.

The effect of muscarinic agonists on the spontaneous release of [3H]GABA was investigated in vitro on rat substantia nigra slices. Acetylcholine (5 x 10(-5) M) in the presence of eserine (5 x 10(-5) M) induced a 12.3% increase of the spontaneous release of [3H]GABA. Similarly, carbachol (5 x 10(-4) M) enhanced by 9% the release of [3H]GABA. This effect was Ca(2+)-dependent, it was abolished in the presence of 0.4 mM Ca2+ and enhanced from 9 to 17% when Ca(2+)-concentration of the superfusion medium was increased from 1.3 to 2.4 mM. The carbachol effect was mediated by muscarinic receptors since it was abolished by atropine (2 x 10(-6) M). The pharmacologically M2 muscarinic receptor subtypes seems to be involved as the carbachol-induced effect was abolished by AF-DX384MS (10(-6) M), an M2 antagonist and was only partially reversed by pirenzepine (10(-5) and 10(-4) M), an M1 antagonist which at these doses also block the M2 receptors. The absence of effect of SCH23390 (10(-6) M) a D1 antagonist as well as the lack of effect of CNQX (10(-5) M) and dizocilpine maleate (10(-6) M), two glutamate antagonists, on the carbachol-induced effect indicated that neither dopamine (through D1 receptors) nor glutamate (through ionotropic receptors) were involved in the response. In addition, the persistence of the carbachol-induced effect in the presence of tetrodotoxin (2 x 10(-7) M) suggests a direct muscarinic-mediated modulation of [3H]GABA. The localization of muscarinic receptors on striatonigral fibres was confirmed by autoradiographic studies showing a decrease of [3H]pirenzepine binding in the substantia nigra after a unilateral striatal lesion induced by kainic acid injection. This latter result provides evidence of the presence of M1 receptors on striatonigral terminals as the concentration of [3H]pirenzepine used (10 nM) is M1-selective. These results indicate a cholinergic modulation of GABA release in the rat substantia nigra mediated by muscarinic receptors localized on striatonigral terminals. The involvement of the m4 muscarinic receptor subtype that have a M1/M2 pharmacology is discussed.

UI	MeSH Term	Description	Entries
D007608	Kainic Acid	(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.	Digenic Acid,Kainate,Acid, Digenic,Acid, Kainic
D008297	Male		Males
D009411	Nerve Endings	Branch-like terminations of NERVE FIBERS, sensory or motor NEURONS. Endings of sensory neurons are the beginnings of afferent pathway to the CENTRAL NERVOUS SYSTEM. Endings of motor neurons are the terminals of axons at the muscle cells. Nerve endings which release neurotransmitters are called PRESYNAPTIC TERMINALS.	Ending, Nerve,Endings, Nerve,Nerve Ending
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
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
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
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
D003712	Dendrites	Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.	Dendrite
D004298	Dopamine	One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.	Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D005680	gamma-Aminobutyric Acid	The most common inhibitory neurotransmitter in the central nervous system.	4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt