Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline.
Presynaptic metabotropic receptors for acetylcholine and adrenaline/noradrenaline were first described more than three decades ago. Molecular cloning has resulted in the identification of five G protein-coupled muscarinic receptors (M(1) - M(5)) which mediate the biological effects of acetylcholine. Nine adrenoceptors (alpha(1ABD),alpha(2ABC),beta(123)) transmit adrenaline/noradrenaline signals between cells. The lack of sufficiently subtype-selective ligands has prevented identification of the physiological role and therapeutic potential of these receptor subtypes for a long time. Recently, mouse lines with targeted deletions for all muscarinic and adrenoceptor genes have been generated. This review summarizes the results from these gene-targeting studies with particular emphasis on presynaptic auto- and heteroreceptor functions of muscarinic and adrenergic receptors. Specific knowledge about the function of receptor subtypes will enhance our understanding of the physiological role of the cholinergic and adrenergic nervous system and open new avenues for subtype-selective therapeutic strategies.
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Albertstrasse 25, 79104, Freiburg, Germany.
Ralf
R
Gilsbach
Lutz
L
Hein
D000322:Adrenergic Agonists / Q000627:therapeutic use; D000818:Animals; D004837:Epinephrine / Q000378:metabolism*; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy / Q000235:genetics; D009638:Norepinephrine / Q000378:metabolism*; D011941:Receptors, Adrenergic / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000322:Adrenergic Agonists; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D017661:Receptors, Presynaptic; D009638:Norepinephrine; D004837:Epinephrine