Histamine smooth muscle effects

Histamine also acts on extravascular smooth muscles to cause contraction or relaxation. Most often, contraction is due to activation of Hj receptors and relaxation to activation of H2 receptors (32). In man, histamine causes contraction of bronchial and intestinal smooth muscles. Histamine-induced contraction of guinea pig ileum is a standard bioassay for histamine. Its effects on smooth muscle of the eye and genitourinary tract are important in some species but not in human ( ). In scombroid poisoning cases. 

It is a powerful antagonist of histamine, antagonizing its effect on smooth muscle of the bronchioles, bladder and partially the intestines and preventing the dilation of capillaries. Promethazine is used in the treatment of allergic reactions. 

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

Epinephrine (adrenalin) 0.1 to 0.5 mg may be given by subcutaneous or intramuscular injection. Hypotension and shock may be treated with fluids and vasopressors. Bronchodilators are given to relax the smooth muscles of the bronchial tubes. Antihistamines may be given to block the effects of histamine. 

There are a number of side-effects of opiates that are due to their actions on opiate receptors outside the central nervous system. Opiates constrict the pupils by acting on the oculomotor nucleus and cause constipation by activating a maintained contraction of the smooth muscle of the gut which reduces motility. This diminished propulsion coupled with opiates reducing secretion in the gut underlie the anti-diarrhoeal effect. Opiates contract sphincters throughout the gastrointestinal tract. Although these effects are predominantly peripheral in origin there are central contributions as well. Morphine can also release histamine from mast cells and this can produce irritation and broncho-spasm in extreme cases. Opiates have minimal cardiovascular effects at therapeutic doses. 

The answer is e. (Hardman, p 587. Katzung, p 270.) Chlorpheniramine is a competitive Hi-re cep tor antagonist that inhibits most responses of smooth muscle to histamine Hrreceptor antagonists have negligible effects on II2 or II3 receptors... 

Activation of brain H receptors also stimulates cGMP synthesis [19]. Outside the brain, histamine is known to relax vascular smooth muscle by activation of endothelial H receptors, thereby increasing endothelial Ca2+ concentrations and stimulating the synthesis and release of nitric oxide. The latter, a diffusible agent, then activates the smooth muscle guanylyl cyclase [30]. Although less is known about these mechanisms in the CNS, there is evidence that brain H receptor activation can produce effects that depend on guanylyl cyclase activity [19]. 

The plasma proteinase, thrombin, a procoagulant enzyme with effects on platelets, endothelial cells and smooth muscle, has been shown to stimulate bone-marrow-derived murine mast cells to release histamine and jS-hexos-aminidase [135]. This secretory response is rapid, reaching a maximum in 1-2 min, and dose-dependent, beginning at about 0.1 U of thrombin and plateauing at 0.5 U thrombin. 

Within 30 minutes of their administration, 6 -adrenergic drugs often reverse most of the functional deficit in Monday morning byssinotics. As there is no mucous secretion, airway smooth muscle contraction is considered the primary response. Exposure of man to histamine aerosols produces pulmonary function changes similar to those seen after exposure to dust extract. However, exposure to histamine aerosol invariably initiates constriction of smooth muscle more rapidly than exposure to cotton dust ( <15 minutes), and dissipates within minutes, while the acute effects of inhalation of cotton dust and dust extracts lasts for hours. The slowly developing and prolonged effects of dust and extracts suggest that mediators other than histamine are involved. 

Potential etiologic agents in cotton dust that release histamine are shown in Table VII. Some of these are effector molecules having potent biological effects in minute concentrations, i.e. peptides, which may act directly to affect chemotaxis and leukocyte recruitment, and also to release histamine and stimulate respiratory smooth muscle contraction. These bifunctional effector molecules are of major importance in considering pathogenic mechanisms in byssinosis. 

Some agents are bifunctional, causing the release of histamine and recruiting leukocytes. Bifunctional mediators include bacterial peptides, endotoxins, DNA, C3a, C5a and bradykinin. Each of these substances can exert dual effects. This may either occur directly, as in the case of bacterial peptides and bradykinin causing chemotaxis and bronchial smooth muscle contraction, or indirectly, as endotoxin and DNA conversion of complement. C3a and C5a act indirectly as complement fragments to effect histamine release, which in turn contracts bronchial smooth muscle. However, both appear to act directly to effect chemotaxis with C5a, the more potent fragment. 

Crude and three diethyl ether extracted, acetone treated, fractions were isolated from large-scale cultures of Gambierdiscus toxicus. Crude extracts at. 04 mg/ml inhibited the histamine contraction response in smooth muscle of the guinea pig ileum. Three semi-purified fractions at 5 ng/ml, effectively inhibited the guinea pig ileum preparation. Two of these fractions followed Michaelis-Menten kinetics for a competitive inhibition. The third fraction inhibited in a non-reversible manner. This study has established the presence of three lipid extracted toxins in toxicus, outlined a method for their assay in small quantities, and identified at least two of the effects of these toxic extracts in animals. 

Phentolamine is also a derivative of imidazoline that exhibits a direct a-adrenoblocking, muscle-relaxant effect on smooth muscle as well as cholinomimetic, histamine, and sympathomimetic effects. The chemical variation of its stmcture permits a few of its properties to be more expressed. For example, the aforementioned tolazoline, 2-benzyl-2-imidazoline, a structural analog of phentolamine, has more of an expressed muscle-relaxant effect on smooth muscle than an a-adrenoblocking effect. 

Two membrane-receptive binding sites called and receptors mediate the pharmacological effect of histamine. Hj receptors are located in smooth muscle of vessels, and bronchial and gastrointestinal tract, while H2 receptors are found in the walls of the stomach, myocardium, and certain vessels. 

At the bronchi, predominantly /32-adrenoceptors are present on the smooth muscle cells. Therefor noradrenaline has hardly any influence on the muscular tonus whereas adrenaline induce a dilatation especially of precontracted bronchi, independent of the cause (histamine, acetylcholine, kinines, prostanoides). This effect can be used therapeutically in the therapy of bronchial asthma. In general the local application by aerosol is more useful than the systemic application, due to lesser side effects and the additional, beneficial effect of the reduction of mucosa swelling. 

The vasodilatory effect of Hi-receptor stimulation is mainly due to an endothelial release of nitric oxide, which is able to activate the soluble guany-late cyclase in vascular smooth muscle cells. This effect is mainly responsible for the erythema seen after injection (insect sting) of histamine. Furthermore, it is responsible, together with the increased capillary permeability, for the cardiovascular symptoms seen in anaphylactic or allergic shock. 

The clinical uses of catecholamines are based on their actions on bronchial smooth muscle, blood vessels, and the heart. Epinephrine is also useful for the treatment of allergic reactions that are due to liberation of histamine in the body, because it produces certain physiological effects opposite to those produced by histamine. It is the primary treatment for anaphylactic shock and is... 

The drugs discussed in this section produce a direct relaxation of vascular smooth muscle and thereby their actions result in vasodilation. This effect is called direct because it does not depend on the innervation of vascular smooth muscle and is not mediated by receptors, such as adrenoceptors, cholinoreceptors, or receptors for histamine, that are acted on by classical transmitters and mediators. 

Succinylcholine acts primarily at the skeletal neuromuscular junction and has little effect at autonomic ganglia or at postganglionic cholinergic (muscarinic) junctions. Actions at these sites attributed to succinylcholine may arise from the effects of choline. Succinylcholine has no direct action on the uterus or other smooth muscle structures. It does not enter the CNS and does not cross the placental barrier. It may, however, release histamine from mast cells. Because succinylcholine works by stimulating rather than blocking end plate receptors, anti-AChEs will not reverse muscle paralysis and may actually prolong the block. 

Histamine is able to cause uterine contraction. Although the magnitude of this effect in humans is normally small, the large amounts of histamine released during anaphylactic reactions can initiate abortion in pregnant women. Histamine can also stimulate contraction of gastrointestinal smooth muscle, with large doses able to produce diarrhea. 

The Lewis triple response illustrates the effects of histamine on vascular smooth muscle, vascular endothelium, and sensory nerve endings. Intradermal injection of as little as 10 jig histamine produces three distinct effects ... 

In medicine and pediatrics, the Hi antagonists are most commonly used for their effects outside the CNS. Outside the CNS they act by blocking the Hi receptors, leading to the inhibition of the following effects of histamine smooth muscle contraction vasoconstriction and, to a lesser degree, the vasodilator effects on en-... 

Have potent direct vasodilator actions on vascular smooth muscle Enhance gastric acid secretion through a histamine-like effect Cause hypotension and bradycardia... 

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