BACKGROUND Pharmaceuticals with targets in the cholinergic transmission have been used for decades and are still fundamental treatments in many diseases and conditions today. Both the transmission and the effects of the somatomotoric and the parasympathetic nervous systems may be targeted by such treatments. Irrespective of the knowledge that the effects of neuronal signalling in the nervous sy...

Muscarinic acetylcholine receptors belong to a superfamily of structurally related proteins which possess seven transmembrane spanning regions and couple to G-proteins [1-4]. Thus far, five distinct muscarinic receptor subtypes (designated ml-m5) are known to exist based on recent molecular cloning studies [2, 5, 6]. Earlier knowledge of muscarinic receptor heterogeneity was based on binding an...

A patient with widespread smooth-muscle disease presented with chronic intestinal pseudo-obstruction but had in addition defects of the bladder, pupils, sweating, and cardiovascular function. There was no evidence of a primary neural lesion, and minor changes in the muscle did not resemble those of a myopathy. In each organ affected muscarinic cholinergic function was at fault, but instead of s...

Acetylcholine and the activation of muscarinic receptors influence the activity of neural networks generating locomotor behavior in the mammalian spinal cord. Using electrical stimulations of the ventral commissure, we show that commissural muscarinic (CM) depolarizations could be induced in lumbar motoneurons. We provide a detailed electrophysiological characterization of the muscarinic recept...

The high-affinity muscarinic antagonist L-[3H]quinuclidinyl benzi-late (L-[3H]QNB) was used to label muscarinic acetylcholine receptors in the astrocyte-enriched fraction isolated from rat hippocampus. Analysis of the saturation and drug inhibition data showed that [3H]QNB binding in the astroglia fraction was saturable, of high affinity (Kd = 0.026 nM) and competitively inhibited by muscarinic...

Previous work from our laboratory indicates that bile acids, specifically lithocholic acid conjugates, interact with muscarinic receptors on gastric chief cells. Structural similarities between acetylcholine and lithocholyltaurine suggest a potential molecular basis for their interaction with the same receptor. We synthesized a hybrid molecule consisting of the steroid nucleus of lithocholyltau...

peripheral (autonomic and somatic) nervous systems. In the autonomic (sympathetic and parasympathetic) nervous system, acetylcholine is released from all preganglionic neurons, as well as from postganglionic parasympathetic neurons. Degradation of acetylcholine by the enzyme acetylcholinesterase occurs in the synapse between the presynaptic and postsynaptic membranes. There are two types of pos...