Aging-related alterations in the contractile responses to acetylcholine, muscarinic cholinoceptors and cholinesterase activities in jejunum and colon of the male Fischer 344 rats

In an attempt to examine whether the muscarinic receptor-activated intestinal function is altered by aging, we studied the changes in (1) contractile responses to acetylcholine (Ach), (2) muscarinic cholinoceptors and (3) cholinesterase (ChE) activities, in jejunum and colon of the young (2-3 months) and aged (24-28 months) Fischer 344 rats. In the physiological contraction experiments of jejunum and colon, Ach concentration-dependently increased the force of contraction, and the contractile responses to Ach were not affected by aging. In addition, the true- and pseudo-ChE activities were not significantly changed by aging. The Ach-induced contraction was competitively inhibited by muscarinic M3-selective antagonist hexahydro-sila-difenidolhydrochloride p-fluoroanalog (p-F-HHSiD), suggesting that the contractile responses in the rat jejunum and colon were mediated through M3-cholinoceptor. Age-related changes in muscarinic cholinoceptors of jejunum and colon were determined with the use of specific muscarinic radioligand [H-3]-quinuclidinylbenzilate (QNB). The [H-3]QNB saturation binding experiments revealed that the maximal binding (B-max) was increased only in aged jejunum without changes in K-D values. These results suggest that aging may not attenuate the Ach-induced intestinal contraction via muscarmic M3 receptor, although the expression of muscarinic cholinoceptor is differentially modulated in jejunum and colon. (C) 2003 Elsevier Inc. All rights reserved.