α₂‐Adrenoceptor‐mediated modulation of the nitrergic innervation of the canine isolated ileocolonic junction

Abstract

1 The effects of specific a-adrenoceptor agonists and antagonists on electrically-evoked non-adrenergic non-cholinergic (NANC) relaxations, previously demonstrated as nitrergic, were investigated in isolated circular muscle strips of the canine ileocolonic junction. 2 During a substance P-induced contraction and in the presence of atropine and guanethidine, the specific a,-adrenoceptor agonist, phenylephrine and antagonist, prazosin, as well as the specific M2-adrenoceptor antagonist, yohimbine, had no effect on the NANC relaxations evoked by electrical field stimulation. In contrast, clonidine and the more specific a2-adrenoceptor agonist, UK-14,304, significantly reduced the electrically-induced relaxations, preferentially those in response to low frequency stimulation. The inhibitory effect of UK-14,304 on these relaxations was antagonized by yohimbine. 3 During a noradrenaline-induced contraction, clonidine, but not UK-14,304 significantly augmented the relaxations to electrical stimulation. 4 The adrenoceptor agonists and antagonists used had no effect on concentration-response curves to NO or on the relaxation induced by nitroglycerin. 5 These results indicate that stimulation of prejunctional a2-adrenoceptors inhibits the nitrergic NANC relaxations induced by field stimulation and thus suggest prejunctional regulation of nitric oxide release via M2-adrenoceptors in the canine ileocolonic junction.

On the origin of rhythmic contractile activity of the esophagus in early achalasia, a clinical case study

“…Transient presynaptic inhibition of nitrergic nerves could be responsible for this, although this has never been demonstrated. Activity of nitrergic nerves can be blocked by presynaptic action (Esplugues, 2002); this has been demonstrated to occur for example via alpha-adrenoceptors in the canine ileocolonic junction (Boeckxstaens et al, 1993), via muscarinic receptors on cerebral perivascular nitrergic nerves (Liu et al, 2002) and varicosities of serotonergic interneurons have been shown to appose nitrergic neurons in the guinea pig small intestine (Neal and Bornstein, 2007). …”

Effects and Mechanisms of Anal Electrical Stimulation on Anorectal Compliance and Tone in Dogs

“…Further studies are needed to explain this discrepancy, although some of previous findings seemed to support the results of this study. [32][33][34][35][36][37][38] Decreased rectal compliance is an important pathophysiologic factor in some patients with incontinence because of the lack of rectal reservoir function, especially if they also have another factor, such as a weak anal sphincter. Substantial decreases in compliance are associated with an increased frequency of stools, rapid transit of stool through the rectum, and increased risk of fecal incontinence.…”

NO as a signalling molecule in the nervous system

“…NO has been linked to the release (Meffert et al ., 1996) of other neurotransmitters and the effects which they produce, in particular acetylcholine (Gustafsson et al ., 1990; Li & Rand, 1989b), noradrenaline (Boeckxstaens et al ., 1993; Li & Rand, 1989a) dopamine (Hanbauer et al ., 1992), glutamate (Montague et al ., 1994; Sorkin, 1993), γ‐aminobutyric acid (GABA) (Beltran et al ., 1999; Kuriyama & Ohkuma, 1995), serotonin (Bogers et al ., 1991; Reiser, 1990b), adenosin triphosphate (ATP) (Boeckxstaens et al ., 1991a), bombesin (Beltran et al ., 1999), carbon monoxide (Xue et al ., 2000), opioids (Barnette et al ., 1990) and endothelin (Reiser, 1990a). The mechanisms responsible for these interactions are still not fully understood, but direct S‐nitrosylation of receptors, activation of cyclic GMP‐dependent protein phosphorylation cascades, regulation of neuronal energy dynamics and a modulating effect on transporters are potentially involved (Choi et al ., 2000; Kiss & Vizi, 2001; Pieper et al ., 2000).…”