Prostaglandin smooth muscle

Many compounds contain more than one functional group Prostaglandin Ei a hormone that regulates the relaxation of smooth muscles con tains two different kinds of carbonyl groups Classify each one (aldehyde ketone carboxylic acid ester amide acyl chloride or acid anhydride) Identify the most acidic proton in prostaglandin Ei and use Table 1 7 to estimate its pK ... 

Reseaich in physiology caiiied out in the 1930s established that the lipid fraction of semen contains small fflnounts of substances that exert powerful effects on smooth muscle. Sheep prostate glands proved to be a convenient source of this material and yielded a mixture of structurally related substances refened to collectively as prostaglandins. We now know that prostaglandins are present in almost all animal tissues, where they cany out a variety of regulatory functions. 

Prostaglandins are a group of lipid autacoids known as eicosanoids. They are produced from membrane phospholipids and found in almost every tissue and body fluid. They are involved in a number of physiological processes including inflammation, smooth muscle tone and gastrointestinal secretion. In the central nervous system they have been reported to produce both excitation and inhibition of neuronal activity. 

The secretion of extracellular matrix proteins is also a function of smooth muscle cells but, since it occurs concurrently with other activities, it does not seem to constitute a physiological state. However, the fraction of the cellular resources which are devoted to it must be regulated these regulatory mechanisms are virtually unknown. In addition, it should be anticipated that autocrine activity occurs as well, involving peptides, prostaglandins, cytokines, and nitric oxide. 

There are several underlying mechanisms responsible for posttransplant HTN. Some causes of HTN in transplant recipients may include renal dysfunction, increased sensitivity to endothelin-1 and angiotensin, increased density of glucocorticoid receptors in the vascular smooth muscle, and decreased production of vasodilatory prostaglandins.57 However, one of the most easily recognized causes of posttransplant HTN is the use of corticosteroids and calcineurin inhibitors.58,59 Corticosteroids usually cause sodium and water retention,57 thus increasing blood pressure, whereas calcineurin inhibitors are associated with a number of effects that may result in HTN, including... 

McGraw DW, Mihlbachler KA, Schwarb MR, et al. Airway smooth muscle prostaglandin-EPl receptors directly modulate beta2-adrenergic receptors within a unique heterodimeric complex. J Clin Invest 2006 116 1400-1409. 

Many hormones and other blood-borne substances (including drugs) also alter contractile activity of smooth muscle. Some of the more important substances include epinephrine norepinephrine angiotensin II vasopressin oxytocin and histamine. Locally produced substances that may alter contraction in the tissue in which they are synthesized include nitric oxide prostaglandins leukotrienes carbon dioxide and hydrogen ion. 

Ragolia, L., et al. (2003). Prostaglandin D2 synthase inhibits the exaggerated growth phenotype of spontaneously hypertensive rat vascular smooth muscle cells. J. Biol. Chem. 278, 22175-81. 

Prostaglandins F2a and E2 (E. J. Corey) members of a family of hormones that mediate blood pressure, smooth muscle contraction, and inflammation (Section 13.11D). 

A guinea pig ileum bioassay was used to detect and aid in the isolation of a smooth-muscle-contracting substance from the Japanese gorgonian coral Euplexaura erecta [108]. This process led to the isolation of prostaglandin F2a (17) from the MeOH extract of the coral. Its identification was based on comparison with authentic PGF2a and its methyl ester by TLC, and comparison with authentic methyl PGF2a trimethylsilyl ether by mass spectrometry. Because of the nature of the techniques employed, some aspects of the stereochemistry in this isolate of PGF2a remain uncertain. 

Mast cell degranulation in response to allergens results in release of mediators such as histamine eosinophil, and neutrophil chemotactic factors leukotrienes C4, D4, and E4 prostaglandins and platelet-activating factor (PAF). Histamine is capable of inducing smooth muscle constriction and bronchospasm and may play a role in mucosal edema and mucus secretion. 

Theophylline and aminophylline may produce bronchodilation by inhibition of phosphodiesterase (thereby increasing cyclic adenosine monophosphate levels), inhibition of calcium ion influx into smooth muscle, prostaglandin antagonism, stimulation of endogenous catecholamines, adenosine receptor antagonism, and inhibition of release of mediators from mast cells and leukocytes. 

Arachidonic acid (C20 4 n-6) is the precursor for the synthesis of prostaglandin molecules (Section 4.4.4), which have a wide range of biochemical effects on for example, the perception of pain, inflammation, blood clotting and smooth muscle contraction. Docosahexaenoic acid (DHA, C22 6) and eicosapentaenoic acid (EPA, C20 5) are both n-3 long-chain polyunsaturated fatty acids (PUFA) which have been shown to have significantly beneficial effects on intellectual development and inflammatory conditions such as asthma and cardiovascular disease. 

SIP induces hsp27 in AlO vascular smooth muscle cells and osteoblasts and amplifies inositol phosphates formation in response to vasopressin and prostaglandin F2c respectively (Kozawa et al, 1999a and b ... 

In mast cells, histamine release induced by IgE or A23187 was also inhibited by feverfew extract [48] which also reduced spasmolytic activity of smooth muscle induced by acetylcholine, 5HT, histamine, prostaglandin E2 and bradykinin [20]. 

Aizawa, H., Inoue, H., Matsumoto, K., Koto, H., Nakano, H., and Kara, N. (1996) Thromboxane A antagonist inhibits leukotriene D -induced smooth muscle contraction in guinea-pig lung parenchyma, but not in trachea. Prostaglandins Leukot. Essent. Fatty Acids. 55,437-440. 

These messengers also play a role in regulating contraction of myometrium, which consists of smooth muscle fibres. Contraction is controlled by increases in the concentration of cytosolic Ca ions. Prostaglandins activate Ca ion channels in the plasma membrane of the fibres oxytocin activates release of Ca from intracellular stores. The increase in concentration of Ca ions leads to activation of myosin light-chain kinase which leads to crossbridge cycling and contraction (as described in Chapter 22 Figure 22.12). 

Fig. 3. Mechanisms of vasocontraction and vasorelaxation in endothelial and smooth muscle cells. COX cyclooxygenase, eNOS endothelial nitric oxide synthase, HO-1 heme oxygenase-1, EET epoxyeicosatrienoic acid, EDHF endothelium-derived hyperpolariz-ing factor, PGI2 prostaglandin I2, NO nitric oxide, CO carbon monoxide, PLC phospholipase C, IP3 inositol 1,4,5-trisphosphate, DAG diacylglycerol, ER/SR endo-plasmic/sarcoplasmic reticulum, AC adenylyl cyclase, cAMP cyclic adenosine monophosphate, sGC soluble guanylyl cyclase, cGMP cyclic guanosine monophosphate.

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