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Aging-Induced Decrease of Cholinergic Response and Calcium Sensitivity on Rat Jejunum Contractions

¹ Department of Pharmacology, Federal University of São Paulo (UNIFESP), Brazil.
² Bogomoletz Institute of Physiology, Kiev, Ukraine.

Address correspondence to Guiomar Silva Lopes, MD, PhD, Rua Três de Maio, 100 São Paulo, 04044-020-Brazil. E-mail: guiolopes{at}terra.com.br

The role of aging on contraction or relaxation through muscarinic or -adrenergic receptors, respectively, was studied in isolated rat jejunum. Furthermore, the influence of extracellular calcium was analyzed, through functional and radioligand binding assays. The rank order of potency for selective muscarinic antagonists for M₁, M₂, and M₃ receptor subtypes, measured from affinity (pA₂) values, was p-fluorohexahydrosiladifenidol (pFHHSiD) (M₃) > pirenzepine (M₁) > methoctramine (M₂), indicating a predominance of M₃ subtype. This order was unchanged with age. Contractions by muscarinic agonist methacholine (MCh) were diminished in aged rats, resulting in lower apparent affinity (pD₂) values, compared with adult controls. A larger decrease of MCh contractions occurred in aged rats after Ca²⁺ withdrawal or after the calcium channel blocker isradipine. Changes were not detected for relaxation by adrenergic agonists. In conclusion, aging caused a decrease of MCh potency, which is probably related to the reduction of calcium sensitivity in jejunum.