1,721,409 research outputs found
Enteric alpha-2 adrenoceptors: pathophysiological implications in functional and inflammatory bowel disorders
No full textThe gastrointestinal tract is innervated by extrinsic noradrenergic nerves which regulate various digestive functions, including mucosal secretions, bowel propulsion and gut sensations, via activation of alpha2-adrenoceptors. These receptors are mostly involved in the prejunctional modulation of enteric neurotransmission, but they act also at extra-neural postjunctional sites. Alpha2-adrenoceptor population consists of distinct subtypes, designated as alpha2A, alpha2B and alpha2C, endowed with different physiological and pharmacological properties, and the attempts to classify alpha2-adrenoceptors at gastrointestinal level have indicated a large predominance of alpha2A subtypes. Studies in humans have shown a favourable influence of alpha2-adrenoceptor activation on colonic tone and sensation, and there is clinical evidence indicating that alpha2-agonists can improve intestinal functions and induce a satisfactory relief of symptoms in patients with irritable bowel syndrome. In addition, genetic investigations have highlighted significant associations of alpha2-adrenoceptor gene polymorphisms with constipation and somatic symptoms in functional disorders of lower digestive tract. Post-operative ileus is a common surgical complication characterized by severe alteration of gut motility, resulting mainly from neurogenic and inflammatory mechanisms. Experiments in models of post-operative ileus have demonstrated an intense expression of alpha2-adrenoceptors in monocytes recruited into the intestinal muscularis, and provided consistent evidence that these receptors promote post-operative gut dysfunctions by hampering enteric neurotransmission and contributing to local inflammatory reaction. Changes in the enteric nervous system are being increasingly recognized also as major determinants of digestive symptoms associated with bowel inflammation. In this regard, studies based on functional and molecular approaches concur in suggesting that the expression of enteric alpha2-adrenoceptors is up-regulated in the presence of intestinal inflammation, and that alpha2-mediated mechanisms are responsible for gut motor alterations occurring at both inflamed and non-inflamed sites. The present review discusses pathophysiological implications of enteric alpha2-adrenoceptors, in the attempt to highlight potential therapeutic applications for drugs targeted on these receptors
SSRIs and birth defects: Can a new statistical approach resolve old controversies?
No full textNO ABSTRACT AVAILABL
The effects of GABA agonists and antagonists on rat gastric acid secretion
No full textAbstract non previsto dalla rivista per questo tipo di articol
Functional evidence that alpha-2A-adrenoceptors are responsible for anti-lipolysis in human abdominal cells
No full textThe effects of alpha 2-adrenoceptor agonists (dexmedetomidine, oxymetazoline), alone or in combination with various alpha-adrenoceptor subtype-selective antagonists (CH-38083, idazoxan, WB4101, BRL44408, ARC-239, prazosin), on noradrenaline- and isoprenaline-induced lipolysis were investigated in human isolated abdominal subcutaneous fat cells. The rank order of potency of antagonists in preventing dexmedetomidine- and oxymetazoline-evoked suppression of isoprenaline-induced lipolysis was (pA2-values): CH-38083 (7.69 and 7.48) congruent to idazoxan (7.5 and 7.41) > BRL44408 (7.23 and 7.19) congruent to WB4101 (7.13 and 7.12) > prazosin (5.18 and 5.17) > ARC-239 (4.72, 4.9). While CH-38083 and idazoxan, non-subtype selective alpha 2-adrenoceptor antagonists and BRL44408, a selective alpha 2A-adrenoceptor antagonist as well as WB4101 potentiated the lipolytic effect of noradrenaline, ARC-239, the selective alpha 2B-adrenoceptor antagonist failed to affect it. In addition since the alpha 2A-adrenoceptor selective agonist, oxymetazoline concentration dependently inhibited the lipolytic effect of isoprenaline, and WB4101 and BRL44408 (alpha 2A-adrenoceptor antagonists) antagonised the effect of oxymetazoline in a competitive manner, it is concluded that the alpha 2A-adrenoceptor subtype is involved in antilipolysis. In addition, functional evidence was obtained that there is an interaction between alpha 2A- and beta-adrenoceptors located on the cell surface of adipocytes, through which locally released noradrenaline and/or circulating circulating adrenaline influence lipolysis
Alpha-2A adrenoceptor subtypes modulate cholinergic contractile activity of guinea-pig ileum
No full textCentral alpha-2 adrenoceptors regulate central and peripheral functions
No full textCentral alpha-2 adrenoceptors regulate a variety of functions including blood pressure, gastrointestinal activity, hormonal secretion, sleep-waking cycle, analgesia, anxiety and some aspects of the withdrawal reaction to opioids. Evidence has been provided that clonidine decreases blood pressure, inhibits salivary secretion and reduces gastrointestinal secretion and motility. Several alpha-2 adrenoceptor agonists reduce wakefulness and inhibit paradoxical sleep, whereas novel imidazoline derivatives, such as detomidine, display sedative and analgesic properties which have been related to the activation of central alpha-2 adrenoceptors. Recent data emphasize the importance of somatodendritic alpha-2 autoreceptors compared to presynaptic alpha-2 autoreceptors as physiological modulators of noradrenergic activity in the central nervous system. In addition, increasing experimental evidence has been provided on the relevant role played by central alpha-2 heteroreceptors (presynaptic and somatodendritic) in the regulation of several functions. Some effects mediated by the activation of alpha-2 adrenoceptors are very similar to those following stimulation of mu opioid receptors. This parallelism can be explained, at least in part, by the presence of these receptors on the same neurons on which they exert an inhibitory action mediated by the same cellular mechanisms. This review resumés the most prominent data about the role played by central alpha-2 adrenoceptors in the regulation of overall functions
Presynaptic alpha2A-adrenoceptor subtypes modulate cholinergic motor responses of guinea-pig ileum
No full textA selective antimuscarinic agent: pirenzepine. Review of its pharmacologic and clinical properties
No full textThe heterogeneity of muscarinic receptors has been well supported by differential characteristics between pirenzepine and atropine both in receptor binding and in whole tissue pharmacology studies. Under these conditions pirenzepine has been classified as a selective receptor antagonist with high affinity for M1 receptors. The antisecretory properties of pirenzepine on gastric acid and pepsin secretion may be attributed to the antagonistic activity of the drug on muscarinic M1 receptors of gastric intramural plexuses, whereas the effect on parietal muscarinic M2 receptors seems of less importance. Additional inhibitory mechanisms on gastric secretion may be represented by pirenzepine-induced increase in somatostatin release from gastrointestinal system. Significant cytoprotective properties of pirenzepine have been observed on a variety of experimentally induced peptic ulcerations. This protective activity may be due to pirenzepine-induced increase in gastric mucosal blood flow as well as to the increase in gastric transmural electric potential difference. In accordance with this pharmacodynamic profile of pirenzepine, numerous clinical studies have revealed its efficacy in the treatment of both duodenal and gastric ulcerations. In addition to this, the clinical usefulness of the drug has been demonstrated in Zollinger-Ellison syndrome, in stress ulceration, in acute gastrointestinal bleeding as well as in gastritis, duodenitis and non-ulcer dyspepsia. In most of the studies pirenzepine has been found to be well tolerated with a low incidence of antimuscarinic effects which may occur at salivary, ocular, cardiac and urinary sites. The clinical use of pirenzepine alone or in association with H2 blockers is recommended in the treatment of peptic ulcer patients, in the case of acute gastrointestinal haemorrhage and in patients non responders to H2 antagonists
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