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Aging-induced decrease of cholinergic response and calcium sensitivity on rat jejunum contractions.

Guiomar Silva Lopes1, Soraya Soubhi Smaili, Afonso Caricati Neto

  • 1Department of Pharmacology, Federal University of São Paulo, São Paulo, Brazil. guiolopes@terra.com.br

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|March 29, 2007
PubMed
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Aging diminishes the potency of methacholine (MCh) contractions in rat jejunum, likely due to reduced calcium sensitivity. Adrenergic relaxation remained unaffected by age.

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Aging Research

Background:

  • The aging process can alter gastrointestinal motility and receptor function.
  • Muscarinic and adrenergic receptors play key roles in regulating jejunal contractility and relaxation.

Purpose of the Study:

  • To investigate the impact of aging on muscarinic and alpha-adrenergic receptor-mediated responses in isolated rat jejunum.
  • To analyze the influence of extracellular calcium on these age-related changes.

Main Methods:

  • Functional assays were used to measure receptor-mediated contractions and relaxations.
  • Radioligand binding assays were employed to determine receptor subtype affinity.
  • Selective muscarinic antagonists were used to characterize receptor subtypes (M(1), M(2), M(3)).

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Main Results:

  • The rank order of muscarinic receptor subtype potency (M(3) > M(1) > M(2)) was consistent in both adult and aged rats, indicating M(3) predominance.
  • Methacholine (MCh)-induced contractions were significantly reduced in aged rats compared to controls.
  • Aged rats showed a greater reduction in MCh contractions following calcium withdrawal or treatment with the calcium channel blocker isradipine.
  • Adrenergic agonist-induced relaxation was not affected by aging.

Conclusions:

  • Aging decreases the potency of methacholine in the rat jejunum.
  • This age-related decrease in potency is likely associated with reduced calcium sensitivity.
  • Aging does not appear to affect alpha-adrenergic receptor-mediated relaxation in the rat jejunum.