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 [3H]-quinuclidinylbenzilate (QNB). The [3H]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 muscarinic M3 receptor, although the expression of muscarinic cholinoceptor is differentially modulated in jejunum and colon.
Tezuka
Asaki
A
Department of Organ Pathophysiology and Internal Medicine, Cardiovascular Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Ishihata
Akira
A
Aita
Tomomi
T
Katano
Yumi
Y
D000109:Acetylcholine / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002802:Cholinesterases / Q000378:metabolism*; D003106:Colon; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D066298:In Vitro Techniques; D007420:Intestine, Large; D007583:Jejunum; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D003959:Diamines; D018727:Muscarinic Antagonists; D010880:Piperidines; C058297:4-fluorohexahydrosiladifenidol; D010890:Pirenzepine; D001285:Atropine; D002802:Cholinesterases; C046773:hexahydrosiladifenidol; D000109:Acetylcholine; C054938:methoctramine