Subject smooth muscle

P-Adrenoceptors have been subdivided into P - and P2-adrenoceptors. A third subset called nontypical P-adrenoceptors or P -adrenoceptors have been described but are stiU the subject of debate. In terms of the interactions with various subsets of P-adrenoceptors, some antagonists are nonselective in that they antagonize the effects of activation of both P - and P2-adrenoceptors, whereas others are selective for either P - or P2-adrenoceptors. P - and P2-adrenoceptors coexist in almost all organs but generally, one type predominates. The focus herein is on the clinically relevant P -adrenoceptor-mediated effects on heart and on P2-adrenoceptor-mediated effects on smooth muscles of blood vessels and bronchioles, the insulin-secreting tissue of the pancreas, and skeletal muscle glycogenolysis for side effects profile (36). 

Smooth muscle contractions are subject to the actions of hormones and related agents. As shown in Figure 17.32, binding of the hormone epinephrine to smooth muscle receptors activates an intracellular adenylyl cyclase reaction that produces cyclic AMP (cAMP). The cAMP serves to activate a protein kinase that phosphorylates the myosin light chain kinase. The phosphorylated MLCK has a lower affinity for the Ca -calmodulin complex and thus is physiologically inactive. Reversal of this inactivation occurs via myosin light chain kinase phosphatase. 

RyRs do not exist as isolated SR ion channels, but as protein complexes subject to modulation by cellular metabolites, [Ca2+] , kinases and other factors (e.g. Marx et al 2000). Currently, very little is known with respect to the expression and localization of RyR isoforms, the regulatory factors underlying sensitivity of the complex to gating, and the effect of luminal (SR) Ca2+ on the probability of spontaneous or triggered release. A renewed focus on the role of RyRs in smooth muscle should help move the field from the initial discovery of these exciting phenomena to a clearer understanding of the function of this system in diverse smooth muscle tissues. 

Furthermore, as well as CaCM-induced phosphorylation, MLCK is also subject to control via a cAMP-dependent protein kinase, PKA. Phosphorylated MLCK binds CaCM only weakly, thus contraction is impaired. This explains the relaxation of smooth muscle when challenged with adrenaline (epinephrine), a hormone whose receptor is functionally linked with adenylyl cyclase (AC), the enzyme that generates cAMP from ATP. 

Mechanisms of action. The tonus of vascular smooth muscle can be decreased by various means. ACE inhibitors, antagonists at ATI-receptors and antagonists at a-adrenoceptors protect against the effects of excitatory mediators such as angiotensin 11 and norepinephrine, respectively. Prostacyclin an-Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Cardiovascular Effects. Palpitations, low blood pressure, and tachycardia were described in subjects exposed to 1,3-DNB by the inhalation (Okubo and Shigeta 1982), oral (Kumar et al. 1990), and dermal (White and Hay 1901) routes of exposure. These responses are consistent with effects of organic nitrates. 1,3-DNB is an organic nitrate and shares many of the cardiovascular properties of therapeutic nitrates. Organic nitrates induce relaxation of the vascular smooth muscle which can result in peripheral vasodilation and a fall in blood pressure followed by a compensatory vasoconstriction (Abrams 1980). The general information available on organic nitrates suggests that exposure to 1,3-DNB or 1,3,5-TNB at ammunition waste sites or at work places where these chemicals are used may lead to adverse cardiovascular effects. 

This question refers to the accompanying graphs. Shown are dose-response curves for isoproterenol (control) both alone and in the presence of one or the other of two -receptor antagonists, drugs X and Y. The responses being measured are an increase in heart rate of a human subject and relaxation of an in vitro strip of human bronchiolar smooth muscle. Drug X is most likely ... 

Another proposed mechanism is inhibition of cell-surface receptors for adenosine. These receptors modulate adenylyl cyclase activity, and adenosine has been shown to provoke contraction of isolated airway smooth muscle and histamine release from airway mast cells. It has been shown, however, that xanthine derivatives devoid of adenosine antagonism (eg, enprofylline) may be potent in inhibiting bronchoconstriction in asthmatic subjects. 

The Hi Receptor and its Ligands. The H receptor mediates effects, through an increase in cyclic adenosine monophosphate (cAMP). such as gastric acid secretion relaxation of airway smooth muscle and of pulmonary vessels increased lower airway mucus secretion esophageal contraclion inhibition of basophil, but not mas cell histamine release inhibition of neutrophil activation and induction or suppressor T cells. There is no evidence that the H- receptor causes significant modulation of lung function in the healthy human subject or in the asthmatic. 

Elastogenesis occurs primarily during late fetal and early neonatal periods. Elastin is synthesized and secreted from several cell types including smooth muscle cells, fibroblasts, endothelial cells, chondroblasts, and mesothelial cells (Uitto et al, 1991) with tissue-specific induction of elastin expression during development (Swee et al, 1995). After elastin has been deposited, its synthesis ceases and very little turnover of elastin is seen during adult life, unless the elastic fibers are subject to injury. In this case,... 

Airway smooth muscle cells isolated from canine tracheae and bronchi subjected to cyclic strain exhibit increased cell number and DNA synthesis in cell culture. The content of total cellular protein, especially contractile proteins including myosin, myosin light chain kinase, and desmin, was increased compared to cells cultured under static conditions. 

The bisbenzylisoquinolines have been the subject of many pharmacological studies, motivated originally by the knowledge that quaternary alkaloids of this type are the active constituents of tube curare. Certain nonquaternary bisbenzylisoquinolines, notably belonging to the curine group, are also smooth muscle re-laxants many bisbenzylisoquinolines are hypotensive, and a few possess anti-... 

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