TY - JOUR
T1 - McN-A-343, a specific agonist of M1-muscarinic receptors, exerts antinicotinic and antimuscarinic effects in the rat adrenal medulla
AU - Wakade, Arun R.
AU - Kahn, Richard
AU - Malhotra, Ravindra K.
AU - Wakade, Chandramohan G.
AU - Wakade, Taruna D.
PY - 1986/12/1
Y1 - 1986/12/1
N2 - Pirenzepine, McN-A-343 and oxotremorine were used to determine the subtypes of muscarinic receptors involved in the secretion of catecholamines from the isolated perfused adrenal gland of the rat. In the presence of 0.1 μM pirenzepine, the concentration-secretion curve for muscarie was shifted in parallel to the right by almost one log unit. With 0.5 μM the shift was over two log units. The apparent dissociation constant for pirenzepine was about 1.12 × 10-8 M. Perfusion with McN-A-343 (1-30 μM) did not evoke the secretion of catecholamines. A further increase to very high concentrations (100-1000 μM) caused only a modest secretion (about 50ng/5 min with 300 μM as compared to the same amount of secretion obatined with 1 μM muscarine). Secretion evoked by nicotine was significantly reduced (30%) by 3 μM McN-A-343, and the inhibition increased (90%) with higher concentrations (100 μM). McN-A-343 also produced concentration-dependent inhibition of catecholamine secretion evoked by muscarine. A significant effect was observed at 30 μM and reached a maximum level at 300 μM. Oxotremorine, like McN-A-343 was a partial agonist on the muscarinic receptors; but unlike McN-A-343, did not block the stimulatory effects of nicotine. Although the pirenzepine data suggest that M1 receptors are responsible for the secretion of catecholamines in the rat adrenal medulla, this conclusion is not supported by the results obtained with the M1-receptor agonist, McN-A-343, which proved to be an effective blocker of muscarinic as well as nicotinic receptors.
AB - Pirenzepine, McN-A-343 and oxotremorine were used to determine the subtypes of muscarinic receptors involved in the secretion of catecholamines from the isolated perfused adrenal gland of the rat. In the presence of 0.1 μM pirenzepine, the concentration-secretion curve for muscarie was shifted in parallel to the right by almost one log unit. With 0.5 μM the shift was over two log units. The apparent dissociation constant for pirenzepine was about 1.12 × 10-8 M. Perfusion with McN-A-343 (1-30 μM) did not evoke the secretion of catecholamines. A further increase to very high concentrations (100-1000 μM) caused only a modest secretion (about 50ng/5 min with 300 μM as compared to the same amount of secretion obatined with 1 μM muscarine). Secretion evoked by nicotine was significantly reduced (30%) by 3 μM McN-A-343, and the inhibition increased (90%) with higher concentrations (100 μM). McN-A-343 also produced concentration-dependent inhibition of catecholamine secretion evoked by muscarine. A significant effect was observed at 30 μM and reached a maximum level at 300 μM. Oxotremorine, like McN-A-343 was a partial agonist on the muscarinic receptors; but unlike McN-A-343, did not block the stimulatory effects of nicotine. Although the pirenzepine data suggest that M1 receptors are responsible for the secretion of catecholamines in the rat adrenal medulla, this conclusion is not supported by the results obtained with the M1-receptor agonist, McN-A-343, which proved to be an effective blocker of muscarinic as well as nicotinic receptors.
UR - http://www.scopus.com/inward/record.url?scp=0022981426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022981426&partnerID=8YFLogxK
U2 - 10.1016/0024-3205(86)90358-9
DO - 10.1016/0024-3205(86)90358-9
M3 - Article
C2 - 2431246
AN - SCOPUS:0022981426
SN - 0024-3205
VL - 39
SP - 2073
EP - 2080
JO - Life sciences
JF - Life sciences
IS - 22
ER -