Muscle tone acetylcholine

Mechanism of Action An acetylcholine antagonist that inhibits the action of acetylcholine by competing with acetylcholine for common binding sites on muscarinic receptors, which are located on exocrine glands, cardiac and smooth-muscle ganglia, and intramural neurons. This action blocks all muscarinic effects. Therapeutic Effect Decreases GI motility and secretory activity, and GU muscle tone (ureter, bladder) produces ophthalmiccycloplegia, and mydriasis. 

Mechanism of Action Anticholinergic alkaloids that inhibit the action of acetylcholine at postganglionic (muscarinic) receptor sites. Morphine (10% of opium) depresses cerebral cortex, hypothalamus, and medullary centers. Therapeutic Effect Decreases digestive secretions, increases GI muscle tone, reduces G1 force, alters pain perception and emotional response to pain. 

Mechanism of Action A cholinergic drug that prevents destruction of acetylcholine by inhibiting the enzyme acetylcholinesterase, thus enhancing impulse transmission across the myoneural junction. Therapeutic Effect Improves intestinal and skeletal muscle tone stimulates salivary and sweat gland secretions. 

Mechanism of Action An anticholinergic that antagonizes the effect of acetylcholine on muscarinic receptors, producing parasympatholyticact ion. Tirerapeutic Effect Reduces smooth muscle tone in the bladder. 

Autonomic nerves can regulate coronary arteriolar tone. Acetylcholine released from postganglionic parasympathetic nerves relaxes coronary arteriolar smooth muscle via the NO/cGMP pathway in humans as described above. Damage to the endothelium, as occurs with atherosclerosis, eliminates this action, and acetylcholine is able to contract arterial smooth muscle and produce vasoconstriction. Skeletal muscle receives sympathetic cholinergic vasodilator nerves, but the view that acetylcholine caused vasodilation in this vascular bed has not been verified experimentally. Moreover, NO, rather than acetylcholine, may be released from neurons. However, this vascular bed responds to exogenous choline esters because of the presence of M3 receptors on endothelial and smooth muscle cells. 

NO has a significant effect on vascular smooth muscle tone and blood pressure. Numerous endothelium-dependent vasodilators, such as acetylcholine and bradykinin, act by increasing intracellular calcium levels, which induces NO synthesis (Figure 19-2). Mice with a knockout mutation in the eNOS gene display increased vascular tone and elevated mean arterial pressure, indicating that eNOS is a fundamental regulator of blood pressure. The effects of vasopressor drugs are increased by inhibition of NOS. 

As well as having an anti-oxidant" and anti-inflammatory effect, DMAE taken orally has been claimed to have many properties an anti-aging effect, improvement of memory and intelligence, increased synthesis of acetylcholine, amelioration of depressive states, improvement in motor coordination, improvement in compulsive, impulsive, hyperactive or antisocial behavior, reduction of chronic fatigue and improvement in the quality of sleep, aid in giving up alcohol and tobacco, reduction of headaches, improved ability to concentrate, improvement in schizophrenia, improved muscle tone, and overall higher energy levels. 

RoBel, A. F Meurs, H., and Zaagsnra, J. (1994), Muscarinic acetylcholine receptors and control of smooth muscle tone. Trends Pharmacol. Sci. 15,407-408. 

Other essential effects of morphine are the elevation of muscle tone in the gastrointestinal tract due to the reduction of acetylcholine liberated from the parasympathetic nerve endings, thus leading to a depression of peristalsis and a reduction in the stretching of the g.i. tract. As a result there is a reduction in stomach emptying and defaecation. The tone of the gall bladder and also of the sphincter muscle of the urinary bladder is also enhanced. 

Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber. Contraction and associated electrical events can be produced by intra-arterial injection of ACh close to the muscle. Since skeletal muscle does not possess inherent myogenic tone, the tone of apparently resting muscle is maintained by spontaneous and intermittent release of ACh. The consequences of spontaneous release at the motor endplate of skeletal muscle are small depolarizations from the quantized release of ACh, termed miniature endplate potentials (MEPPs) [15] (seeCh. 10). Decay times for the MEPPs range between l and 2 ms, a duration similar to the mean channel open time seen with ACh stimulation of individual receptor molecules. Stimulation of the motoneuron results in the release of several hundred quanta of ACh. The summation of MEPPs gives rise to a postsynaptic excitatory potential (PSEP),... 

Carbachol is a powerful cholinic ester that stimulates both muscarinic and nicotinic receptors, as well as exhibits all of the pharmacological properties of acetylcholine while in addition resulting in vasodilation, a decrease in heart rate, an increase in tone and con-tractability of smooth muscle, stimulation of salivary, ocular, and sweat glands as well as autonomic ganglia and skeletal muscle. For this reason, use of carbachol, like acetylcholine, is limited. The exception is that it is used in ophthalmological practice and post-operational intestines and bladder atony. Upon administration in the eye, the pupil constricts and the intraocular pressure is reduced. It is used for severe chronic glaucoma. Synonyms of this drag are doryl and miostat. 

Beside this there are some major differences with the neurotransmission in the autonomous nervous system The contractile activity of the skeletal muscle is almost completely dependent on the innervation. There is no basal tone and a loss of the innervation is identical to a total loss in function of the particular skeletal muscle. In contrast to the target organs of the parasympathetic nervous system the skeletal muscle cells only have acetylcholine receptors at the site of the so-called end-plate, the connection between neuron and muscle cell with the rest of the cell surface being insensitive to the transmitter. The release of acetylcholine results in a postjunctional depolarization which is either above the threshold to induce an action potential and a contraction or below the threshold with no contractile response at all. In contrast to the graduated reactions of the parasympathetic target organs, this is an all or nothing transmission. 

Effect on smooth muscles Acetylcholine causes increase in tone, amplitude of contractions, peristalsis and secretory activity of the gastrointestinal tract. It causes contraction of smooth muscles of gall bladder and relaxation of sphincters of gastrointestinal and biliary tract. 

Other actions In the gastrointestinal tract, acetylcholine increases salivary secretion, and stimulates intestinal secretions and motility. Bronchiolar secretions are also stimulated. In the genitourinary tract, the tone of the detrusor urinae muscle is increased. In the eye, acetylcholine is involved in stimulating ciliary muscle contraction for near vision and in the constriction of the pupillae sphincter muscle, causing miosis (marked constriction of the pupil). 

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