Differential Effects of Maturation on Nicotinic- and Muscarinic Receptor-Induced Ion Secretion in Guinea Pig Distal Colon

Powell, Adrianne R.; Reddix, Rhoda A.

doi:10.1046/j.1525-1373.2000.22413.x

Cited by 12 publications

(7 citation statements)

References 13 publications

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“…Additionally, whereas cholinergic control of enteric epithelial ion transport is, under normal circumstances, dominated by M 3 and M 1 mAChRs (lack of involvement of M 2 and M 4 mAChR subtypes is generally inferred from pharmacological data, but has never been directly proven, and M 5 mAChR involvement has not been addressed), the modulating effect of nAChRs should be better characterized, as should cholinergic neuronal interactions within the submucosa and between the submucosal and myenteric plexuses. Finally, in segments of rabbit small intestine containing Peyers's patches, CCh evoked a decrease rather than an increase in I SC (Brayden and Baird, 1994) and greater involvement of nAChR has been implicated in colonic tissue from young compared to mature guinea‐pigs (Powell and Reddix, 2000); thus, whereas the majority of our understanding of the control of enteric epithelial ion transport has been gleaned from analyses of tissues from adult animals, there is value in considering tissue from infants/young animals and from those with an enhanced complement of immune cells (see below).…”

Section: Cholinergic Control Of Enteric Epithelial Ion Transportmentioning

confidence: 99%

Cholinergic regulation of epithelial ion transport in the mammalian intestine

Hirota

McKay

2006

British J Pharmacology

119

110

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Acetylcholine (ACh) is critical in controlling epithelial ion transport and hence water movements for gut hydration. Here we review the mechanism of cholinergic control of epithelial ion transport across the mammalian intestine. The cholinergic nervous system affects basal ion flux and can evoke increased active ion transport events. Most studies rely on measuring increases in short-circuit current (I SC ¼ active ion transport) evoked by adding ACh or cholinomimetics to intestinal tissue mounted in Ussing chambers. Despite subtle species and gut regional differences, most data indicate that, under normal circumstances, the effect of ACh on intestinal ion transport is mainly an increase in Cl -secretion due to interaction with epithelial M 3 muscarinic ACh receptors (mAChRs) and, to a lesser extent, neuronal M 1 mAChRs; however, AChR pharmacology has been plagued by a lack of good receptor subtype-selective compounds. Mice lacking M 3 mAChRs display intact cholinergically-mediated intestinal ion transport, suggesting a possible compensatory mechanism. Inflamed tissues often display perturbations in the enteric cholinergic system and reduced intestinal ion transport responses to cholinomimetics. The mechanism(s) underlying this hyporesponsiveness are not fully defined. Inflammation-evoked loss of mAChR-mediated control of epithelial ion transport in the mouse reveals a role for neuronal nicotinic AChRs, representing a hitherto unappreciated braking system to limit ACh-evoked Cl -secretion. We suggest that: i) pharmacological analyses should be supported by the use of more selective compounds and supplemented with molecular biology techniques targeting specific ACh receptors and signalling molecules, and ii) assessment of ion transport in normal tissue must be complemented with investigations of tissues from patients or animals with intestinal disease to reveal control mechanisms that may go undetected by focusing on healthy tissue only.

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Section: Cholinergic Control Of Enteric Epithelial Ion Transportmentioning

confidence: 99%

Cholinergic regulation of epithelial ion transport in the mammalian intestine

Hirota

McKay

2006

British J Pharmacology

119

110

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“…Neuromuscular events must be coordinated with mucosal function in order for GI motility to occur in a normal fashion. Recent studies have shown that spontaneous, neurally mediated secretory activity in the colon of young guinea‐pigs is reduced or absent in older animals 27 …”

Section: Age‐related Loss Of Enteric Intrinsic Sensory Neuronesmentioning

confidence: 99%

Neurodegeneration: a key factor in the ageing gut

Wade

Cowen

2004

Neurogastroenterology Motil

109

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Many individuals experience gastrointestinal (GI) dysfunction more frequently as they age, and the segment of the human population that is growing the most rapidly is the 'oldest old', who are ‡ 80 years old. There has recently been renewed interest in the age-related changes intrinsic to the gut, and these investigations may help physicians understand the 'normal' aged GI tract, as distinct from disordered bowel function that is the result of comorbid conditions and/or GI side effects of medications used to treat those conditions. In this concise review we summarize recent data that suggest age-related neurodegenerative changes in the enteric nervous system (ENS) are key to functional changes observed with advanced age. Morphological studies are reviewed that demonstrate clearly the loss of enteric neurones in both submucosal and myenteric plexuses in humans and in rodents. Recent studies that indicate selective preservation of nitrergic, but not cholinergic, neurones are reviewed, as are preliminary findings that intrinsic sensory neurones may be among the most 'age-labile' subpopulations of the ENS. Caloric restriction remains the only intervention known that prevents neurodegeneration of ageing in the ENS, and mechanisms involved in this phenomenon are discussed. The field of ageing research in enteric neurobiology is ripe for rapid progression from phenomenology of age-related losses of neurones and associated functional changes to discovery of therapeutic approaches that may help ameliorate deterioration of bowel function and thereby contribute significantly to improved quality of life in advanced age.

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“…As outlined above, researchers have now begun to answer many of these questions. There is evidence that specific neuronal phenotypes may be more vulnerable to the aging process than others (28,36,39,40), that neuronal N-type Ca 2ϩ channels may be functionally impaired in the ENS (27), that there may be a decline in the ability of inhibitory motor neurons to synthesize NO (36), and that there may be a decrease in the expression or function of submucosal nicotinic receptors (26). There are clearly many unanswered questions, and these studies exemplify the future directions in which this field can rapidly advance.…”

Section: Mucosal Functionmentioning

confidence: 99%

I. Age-related changes in the enteric nervous system

Wade

2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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As we enter the 21st century, the segment of the population that is the most rapidly expanding is that comprised of individuals 85 yr of age and older. Dysfunctions of the gastrointestinal (GI) system, including dysphagia, constipation, diarrhea, and irritable bowel syndrome are more common complaints of the elderly, yet our knowledge of the aging GI tract is incomplete. Compared with the rapid advances in the neurobiology of aging in the central nervous system, the understanding of age-related changes in the enteric nervous system (ENS) is poor. In this brief review, I recap experiments that reveal neurodegenerative changes and their functional correlates in the ENS of mice, rats, and guinea pigs. Clinical literature seems indicative of similar structural and functional age-related changes in the human ENS. Current studies that address the mechanisms underlying age-related changes in the ENS are introduced. The future directions for this field include physiological and pharmacological studies, especially at cellular and molecular levels. Research in the aging ENS is poised to make major advances, and this new knowledge will be useful for clinicians seeking to better understand and treat GI dysfunction in the elderly.

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Differential Effects of Maturation on Nicotinic- and Muscarinic Receptor-Induced Ion Secretion in Guinea Pig Distal Colon

Cited by 12 publications

References 13 publications

Cholinergic regulation of epithelial ion transport in the mammalian intestine

Cholinergic regulation of epithelial ion transport in the mammalian intestine

Neurodegeneration: a key factor in the ageing gut

I. Age-related changes in the enteric nervous system

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