β-Adrenoceptors, but not dopamine receptors, mediate dopamine-induced ion transport in late distal colon of rats

Abstract

Dopamine, an important modulator in the gastrointestinal system, induces concentration-dependent transepithelial ion transport in the distal colon of the rat, as shown by a decrease in the short-circuit current, and acts in a segmentally dependent manner. However, the receptor(s) that mediates dopamine-induced ion transport is unknown. We have investigated the receptor mechanisms underlying dopamine-induced colonic ion transport by means of short-circuit current recording, real-time polymerase chain reaction, and Western blotting analysis, plus gene transfection and enzyme-linked immunosorbance assay. mRNA transcripts of adrenoceptors (alpha, beta) and dopaminergic receptors (D(1) and D(2)) were detected in the rat late distal colonic mucosa, with beta(2) displaying the highest expression. A similar result was found in human colorectal mucosa (equivalent of late distal colon in rat). Pretreatment with a beta(1)-adrenoceptor antagonist (CGP-20712A) and a beta(2)-adrenoceptor antagonist (ICI 118,551) inhibited the dopamine-induced short-circuit current response by 52.59% and 92.51%, respectively. However, neither dopamine D(1) receptor antagonist SCH-23390 nor dopamine D(2) receptor antagonist sulpiride blocked the effect of dopamine. Protein expression of both beta(1)- and beta(2)-adrenoceptors was found in the mucosa of rat distal colon and human sigmoid colon and rectum. Dopamine significantly increased intracellular cAMP levels in COS-7 cells transfected with beta(1)- or beta(2)-adrenoceptors. Thus, beta-adrenoceptors (mainly beta(2)-adrenoceptors), but not dopamine receptors, mediate dopamine-induced ion transport in the late distal colon of the rat. This extends our knowledge of the late distal colon (rats) or colorectum (human) and provides further experimental evidence that might aid the prevention, diagnosis, and clinical therapy of human colorectal diseases.

Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine–induced Parkinson's disease rats

“…24 Moreover, b-ARs mediate the effect of DA on GI function in rats and the anti-inflammatory effect of DA on cell lines. 27,35 We suppose that the upregulation of b 3 -ARs may regulate not only NE, but also the higher dose of DA, which may be the one of factors inducing the colonic dysmotility in 6-OHDA rats.…”

“…Several studies have demonstrated crosstalk between the dopaminergic system and adrenergic system. 27,28 It is unclear whether the adrenergic system in the colon is altered in 6-OHDA rats. NE at 10 nM, 100 nM, and 1 mM in a dose-dependent manner inhibited colonic motility in control rats, which was blocked by the selective b 3 -AR antagonist SR59230A at a dose of 1.0 3 10 25 mol/L (Fig 3, A and B).…”

Stress at the intestinal surface: catecholamines and mucosa–bacteria interactions

“…These effects are generally mediated by alpha-adrenergic receptors located on enteric neurons projecting to the epithelium or the epithelial cells per se (Field and McColl 1973;Chang et al 1983;Dharmsathaphorn et al 1984;Fondacaro et al 1988;Hildebrand et al 1993). In the colon, however, these catecholamines can act on alpha-or beta-adrenergic receptors to evoke potassium, bicarbonate or chloride secretion depending upon mammalian species and colonic segment (Sullivan and Smith 1986;Sellin and De Soignie 1987;Hörger et al 1998;Lam et al 2003;Zhang et al 2008;Halm et al 2010).…”

Response of colonic motility to dopaminergic stimulation is subverted in rats with nigrostriatal lesion: relevance to gastrointestinal dysfunctions in Parkinson's disease

“…Indeed, dopaminergic blockers (domperidone, for example) are used as GI prokinetics, as they antagonize DA inhibitory effects on GI motility, by blocking DRD2 . A further element of complexity is added by the observation that, in the GI, DA is able to activate adrenergic (alpha and beta) receptors to modulate, for example, motility in the small intestine and ion transport in the distal colon …”