Vascular mascarinic receptors: characterization in cerebral and peripheral arteries

Vascular muscarinic receptors: characterization in cerebral and peripheral arteries DucHes, S.P., Garcia-Villal6n *, A.L. a n d Krause, D . N . D~ot. of Pharmm'olo~; Colleo~eof Medicine, U~iversity of California, lrvine, CA, U.S.A. and * Dept. de Fisiologia, Facultad de Medicina, UniversidadAutonoma, 28029 Madri~ Spain

Muscarinic recepto~ were pharmacologically characterized in peripheral and cerebral vascular preparations, using both a functional bioassay ~ d radioligand binding technique. Isometric contractile responses of isolated ring segments were measured in three ts]~es of arteries: the bovine coronary artery, in which contraction to muscarinic agonists is independent of the endothelium, and the rabbit ear and basilar mter;es, which manifest an endothelium-dependent relaxation to muscarinic stimulation. These tissues were compared with bovine pial arteries, in which specific binding of the muscarinic ligand [3Hlquinuclidinyl benzilate (QNB) was characterized. In bovine pial arteries, muscarinic receptor agonists did not produce Antagonist

pK n

pK,

Bovine corcaa,-y

Rabbit ear

Rabbit basilar

Bovine pial

Pirenzepine AF-DX 116 Dicydomine 4-DAMP Methoctramine HHS

6.9 6.3 7.7 9.2 5.8 8.5

6.7 6.0 7.6 8.9 5.5 8.2

7.5 6.3 8.3 6.5 8.2

6.2 6.8 7.0 7.7 6.8 6.4

4-DAMP, 4-diphenylacetoxy-N-methyipiperidine methobromide; HHS, hexahydrosiladifenidol. significant relaxation or contraction, but did evoke an increase in phosphoinositide turnover. As demonstrated by antagonist pK n values for inhibition of responses to methacholine, both endothelial-dependent responses (rabbit ear and basilar arteries) and the non-endothelium dependent rcsponse of the bovine coronary artery have similar pharmacological characteristics. All three tissues appear to possess M 3 receptors. In contrast, in bovine pial arteries pK i values for inlubifion of [3H]QNB binding appear similar to M a receptors. However these receptors do not appear to mediate any direct vasomotor responses. Thus, in peripheral blood vessels, endothelial and smooth muscle muscarinic receptors may belong to the same, M3, class. In the cerebral circulation, endothelial receptors also appear to be M 3, but receptors studied by ligand binding in pial artery membranes, most likely reflecting non-contractUe smooth muscle sites, seem to be of the M a subtype. Supported by NIH # DK36289. P.th.392 [

Preferential reduction of acetylcholine-receptors in facial muscles of 'myasthenic' rats Plomp, J.J., van K e m p e n , G . T h . H . a n d Molenaar, P.C. Department of Pharmacology, University of Leiden, Leiden, The Netherlands

Myasthenia gravis (MG) is an autoimmune disease in which antibodies directed against the acetylcholine (ACh) receptor cause weakness of skeletal muscles. In myasthenia gravis the muscles of the face are generally affected more than other skeler,~ muscles of the patient. It is possible that this is due to a relatively small safety factor of neu:orauscular t~.ansmission in these muscles. Alternatively, it could be that the anti-ACh-receptor antibodies have a