Bradley, Karen and Rowan, Edward and Harvey, Alan L. (2001) Effects of brucine, a plant alkaloid, on M(1) muscarinic receptors and alpha(1)-adrenoceptors in the rabbit vas deferens preparation. Toxicon, 39 (4). pp. 581-587.Full text not available in this repository. (Request a copy from the Strathclyde author)
The plant alkaloid brucine is an analogue of strychnine and is known to be an allosteric modulator at cloned M1 muscarinic receptors. The functional effects of brucine were examined on the M1 muscarinic receptors in the rabbit isolated vas deferens preparation. Brucine (10-100 μM) enhanced the effects of the muscarinic agonist McN-A-343 at presynaptic M1 muscarinic receptors in the rabbit isolated vas deferens preparation, but only when brucine was added prior to McN-A-343. This effect is indicative of a positive allosteric action. It was poorly reversed on washing. Brucine did not affect the responses to the mamba venom muscarinic toxins MT2 and MT4, which are also allosteric activators in this preparation. Brucine (10-100 μM) caused a significant decrease in the twitch response to electrical stimulation in the rabbit vas deferens preparation, which was not antagonised by 100 nM pirenzepine (an M1 muscarinic antagonist). Brucine and MT4, but not MT2, caused significant decreases (p<0.05) in the responses to noradrenaline in the rabbit vas deferens preparation. Responses to ATP and KCl were not affected. In radioligand binding assays, brucine displaced the α1-adrenoceptor ligand prazosin from its specific binding sites in membranes made from rat cerebral cortex and rat vas deferens. The apparent Ki values were 150 and 3.4 μM in the cortical and vas deferens membranes, respectively. The positive allosterism found with brucine at cloned M1 receptors seems to be mirrored at native M1 receptors. However, the unexpected blocking effects at α1-adrenoceptors indicates that more selective ligands than brucine are required as starting points for the design of specific enhancers of the activity of M1 receptors with therapeutic potential.
|Keywords:||brucine, muscarinic cholinoceptors, adrenoceptors, muscarinic toxins, allosterism, prazosin, transmitter release, Pharmacy and materia medica, Toxicology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Strathprints Administrator|
|Date Deposited:||28 Apr 2010 09:14|
|Last modified:||04 May 2016 14:19|