Smooth Muscle Effects

The opposing effects on smooth muscle (A) of a- and p-adrenoceptor activation are due to differences in signal transduction, ai -Receptor stimulation leads to intracellular release of Ca2+ via activation of the inositol trisphosphate (IP3) pathway. In concert with the protein calmodulin, Ca2+ can activate myosin kinase, leading to a rise in tonus via phosphorylation of the contractile protein myosin (— vasoconstriction). 012-Adrenoceptors can also elicit a contraction of smooth muscle cells by activating phospholipase C (PLC) via the py-subunits of G, proteins. 

Vasoconstriction induced by local application of a-sympathomimetics can be employed in infiltration anesthesia (p.204) or for nasal decongestion (naphazoline, tetra-hydrozoline, xylometazoline p.94, 336, 338). Systemically administered epinephrine is important in the treatment of anaphylactic shock and cardiac arrest. 

Bronchodilation. p2-Adrenoceptor-medi-ated bronchodilation plays an essential part in the treatment of bronchial asthma and chronic obstructive lung disease (p.340). For this purpose, p2-agonists are usually given by inhalation preferred agents being those with low oral bioavailability and low risk of systemic unwanted effects (e. g., feno-terol, salbutamol, terbutaline). 

Tocolysis. The uterine relaxant effect of p2-adrenoceptor agonists, such as fenoterol, can be used to prevent premature labor. p2-Vaso-dilation in the mother with an imminent drop in systemic blood pressure results in reflex tachycardia, which is also due in part to the p -stimulant action of these drugs. 

By stimulating p-receptors, and hence cAMP production, catecholamines augment all heart functions including systolic force, velocity of myocyte shortening, sinoatrial rate, conduction velocity, and excitability. In pacemaker fibers, cAMP-gated channels ( pacemaker channels ) are activated, whereby diastolic depolarization is hastened and the firing threshold for the action potential is reached sooner (B). cAMP activates protein kinase A, which phosphorylates different Ca2+ transport proteins. In this way, contraction of heart muscle cells is accelerated, as more Ca2 enters the cell from the extracellular space via L-type Ca2 channels and release of Ca2 from the sarcoplasmic reticulum (via ryanodine receptors, RyR) is augmented. Faster relaxation of heart muscle cells is effected by phosphorylation of troponin and phospholamban. 

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Vagal neuropathy in diabetes mellitus [145, 146] and truncal vagotomy [147] may markedly change intestinal motility, as do heart-lung transplantation [148]. Spinal cord lesions also alter gut function, but the outlet obstruction due to failure of the striated muscles involved in defecation is more important than the enteric smooth muscle effects [149]. 

Smooth muscles Receptor interactions and smooth muscle effects... 

The postsynaptic physiological effects of serotonin are varied and widespread. The administration of serotonin leads to powerful smooth-muscle effects in the cardiovascular and gastrointestinal systems. Vasodilation and hypotension may result, partly through central effects, if the serotonin concentration in the CNS is increased by administration of the serotonin precursor 5-hydroxytryptophan. Unlike serotonin, this precursor can cross the blood-brain barrier. Intestinal mobility is also influenced by serotonin. 

Important differences in vascular selectivity exist among the calcium channel blockers. In general, the dihydropyridines have a greater ratio of vascular smooth muscle effects relative to cardiac effects than do diltiazem and verapamil. Furthermore, the dihydropyridines may differ in their potency in different vascular beds. For example, nimodipine is claimed to be particularly selective for cerebral blood vessels. Splice variants in the structure of the cq channel subunit appear to account for these differences. 

Cyproheptadine resembles the phenothiazine antihistaminic agents in chemical structure and has potent H receptor-blocking as well as 5-HT2-blocking actions. The actions of cyproheptadine are predictable from its histamine and 5-HT receptor affinities. It prevents the smooth muscle effects of both amines but has no effect on the gastric secretion stimulated by histamine. It also has significant antimuscarinic effects and causes sedation. 

The methylxanthines have effects on the central nervous system, kidney, and cardiac and skeletal muscle as well as smooth muscle. Of the three agents, theophylline is most selective in its smooth muscle effects, whereas caffeine has the most marked central nervous system effects. 

Wang, X.-L. Akhtar, R.A. Abdel-Latif, A.A. Purification and properties of D-myo-inositol 1,4,5-trisphosphate 3-kinase from bovine iris sphincter smooth muscle effect,s of protein phosphorylation in vitro and in intact muscle. Biochem. J., 308 (Pt 3), 1009-1016 (1995)... 

In general, when morphine is used and the smooth muscle effects are objectionable, atropine may be given simultaneously to antagonise spasm. Unfortunately this does not always effectively oppose the rise of pressure induced in the biliary system, nor does it restore bowel peristalsis. Glyceryl trinitrate will relax morphine-induced spasm. 

Application of the knowledge of the electrophysiologic, negative inotropic, and vascular smooth muscle effects of calcium inhibitory compounds in isolated tissue preparations to normal and diseased animals or human patients is difficult. 

Winder SJ, Allen EG, Fraser ED, Kang HM, Kargacin GJ, Walsh MP (1993) Calponin phosphorylation in vitro and in intact muscle. Biochem J 296 827-836 Winder SJ, Pato MD, Walsh MP (1992) Purification and characterization of calponin phosphatase from smooth muscle. Effect of dephosphorylation on calponin function. Biochem J 286 197-203... 

Which of the following dmgs can reverse one or more smooth muscle effects of circulating histamine in humans ... 

Chemistry, mechanism, and effects Glucagon is the product of the A cells of the endocrine pancreas. Like insulin, glucagon is a peptide but unlike insulin, glucagon acts on G protein-coupled receptors. Activation of glucagon receptors, which are located in heart, smooth muscle, and liver, stimulates adenylyl cyclase and increases intracellular cAMP. This results in increases in the heart rate and the force of contraction, increased hepatic glycogenolysis and gluconeogenesis and relaxation of smooth muscle. The smooth muscle effect is particularly marked in the gut. 

Indirectly acting sympathomimetic like amphetamine but less CNS stimulation, mote smooth muscle effects. In botanicals (eg, Ma-huang). Tox hypertension, stroke, MI. 

LTC4, LTD4 and LTE4 (possibly also the 1 -trans isomers) fulfill two iihportant biological criteria previously attributed to the pathophysiological agent SRS-A, i.e. the potent smooth muscle effects preferentially in peripheral human airways and the marked increase of vascular permeability in the venules. 

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