Sweat glands, muscarinic receptor

Figure 9.2 Autonomic nerve pathways. All preganglionic neurons release acetylcholine (Ach), which binds to nicotinic receptors (N) on the postganglionic neurons. All postganglionic neurons in the parasympathetic system and some sympathetic postganglionic neurons innervating sweat glands release Ach that binds to muscarinic (M) receptors on the cells of the effector tissue. The remaining postganglionic neurons of the sympathetic system release norepinephrine (NE), which binds to alpha (a) or beta (P) receptors on cells of the effector tissue. The cells of the adrenal medulla, which are modified postganglionic neurons in the sympathetic system, release epinephrine (EPI) and NE into the circulation.

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. 

Atropine, an alkaloid from Atropa belladonna, is the classical parasympatholytic compound. It competes with acetylcholine for the binding at the muscarinic receptor. Its affinity towards nicotinic receptors is very low, so that it does not interfere with the ganglionic transmission or the neuromotor transmission, at least in therapeutic dosages. However, in the central nervous system muscarinic receptor do play an important role and while atropine can penetrate the blood-brain barrier it exerts pronounced central effects. Atropine, like all other antagonists of the muscarinic acetylcholine receptor inhibit the stimulatory influence of the parasympathetic branch of the autonomous nervous system. All excretory glands (tear, sweat, salivary, gasto-intestinal, bronchi) are... 

Mechanism of Action A G1 ant ispasmodic and ant ichol inergic agent that inhibits the action of acetylcholine at postganglionic (muscarinic) receptor sites. Therapeutic Effect Decreases secretions (bronchial, salivary, sweat gland) and gastric juices and reduces motility of G1 and urinary tract. 

Stimulation of the parasympathetic nervous system modifies the organ functions by two main pathways. Firstly, the acetylcholine released from parasympathetic nerves can activate muscarinic receptors which are present in gland cells (sweat glands), smooth muscles and heart. The... 

Atropine suppresses thermoregulatory sweating. Sympathetic cholinergic fibers innervate eccrine sweat glands, and their muscarinic receptors are readily accessible to antimuscarinic drugs. In adults, body temperature is elevated by this effect only if large doses are administered, but in infants and children even ordinary doses may cause "atropine fever."... 

The toxic effects can be divided into three types as the accumulation of acetylcholine leads to symptoms that mimic the muscarinic, nicotinic, and CNS actions of acetylcholine. Muscarinic receptors for acetylcholine are found in smooth muscles, the heart, and exocrine glands. Therefore, the signs and symptoms are tightness of the chest, wheezing due to bronchoconstriction, bradycardia, and constriction of the pupils (miosis). Salivation, lacrimation, and sweating are all increased, and peristalsis is increased, leading to nausea, vomiting, and diarrhea. 

Sweating is stimulated by direct action of the increased endogenous acetylcholine on muscarinic receptors of sweat glands in the skin these glands are innervated by the sympathetic division of the autonomic nervous system. Agitation is produced by a central excitatory effect on cholinergic neurones in the brain, but in large doses anticholinesterases can cause depression of the respiratory centre in the medulla. 

Muscarinic acetylcholine receptors occur in the target tissues. They are mostly found in parasympathetic s mapses, but they also occur in the sympathetically innervated sweat glands. 

Muscarinic receptors play an essential role in regulating the functions of organs innervated by the autonomic nervous system to maintain homeostasis of the organi.sm. The action of ACh on muscarinic receptors con re.sull in. stimulation or inhibition of the organ system affected. ACh stimulates secretions from salivary and sweat glands, secretions and contraction of the gut. and constriction of the airways of the respiratory tract. It inhibits contraction of the heart and relaxes smooth muscle of blood vc.ssels. 

BZ is a competitive inhibitor of muscarinic receptors associated with the parasympathetic nervous system that innervate the eyes, heart, respiratory system, skin, gastrointestinal tract, and bladder. The sweat glands, innervated by the sympathetic nervous system, are also modulated by muscarinic receptors. By any route of exposure, the onset of action is approximately 1 h, with peak effects occurring 8h postexposure. Signs and symptoms gradually subside over 2-4 days. Most of the absorbed BZ is excreted via the kidney. 

M 3—Muscarinic receptors are located on all organs and tissues innervated by postganglionic nerves of the PANS and on thermoregulatory sweat glands innervated by the SANS. 

The major receptor types are ganglionic nicotinic (N ), endplate nicotinic (NM), muscarinic and adrenergic receptor of four major subtypes (a,, p, P2). ACh is the neurotransmitter at all N receptors, at the M receptors innervated by postganglionic fibers of the PANS, and the thermoregulatory sweat glands innervated by the SANS. Norepinephrine (NE) is the neurotransmitter at adrenoreceptors innervated by the SANS. NE and epinephrine (E) are released from the adrenal medulla. Dopamine (DA) receptor activation leads to vasodilation in some vascular beds. 

Uninnervated receptors Some receptors that respond to autonomic transmitters and drugs receive no innervation. These include muscarinic receptore on the endothelium of blood vessels, some presynaptic receptors, and, in some species, the adrenoceptors on apocrine sweat glands and a, and P adrenoceptors in some blood vessels. 

Although atropine is a known antidote against several toxic substances, its overdose can cause severe poisoning. As with other tropane alkaloids, atropine competitively blocks muscarinic acetylcholine receptor sites. This results in dilation of the pupil of the eye (mydriatic effect), dryness of the mucous membranes, especially of the mouth, and inhibition of activity of sweat glands (parasympatholytic action). At toxic doses, it causes palpitation, speech disturbance. 

S)-Hyoscyamine and (6)-scopolamine are esters of the amino alcohols tropine and scopine with ( S)-tropic acid, which is derived from phenylalanine (Fig. 3). The two alkaloids occur exclusively in the Solanaceae family. They act as antagonists of muscarinic acetylcholine receptors (parasympatholytics) and lead to an increase in pulse rate, relaxation of smooth muscles, e.g., in the gastrointestine and the bronchial tract, reduction of salivary, bronchial, gastric, and sweat gland secretion. While hyoscyamine is a central stimulant, scopolamine depresses the central nervous system. 

A. Anticholinergic agents competitively antagonize the effects of acetylcholine at peripheral muscarinic and central receptors. Exocrine glands, such as those responsible for sweating and salivation, and smooth muscle are mostly affected. The Inhibition of muscarinic activity in the heart leads to a rapid heart beat. 

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