Aging-induced decrease of cholinergic response and calcium sensitivity on rat jejunum contractions.
The role of aging on contraction or relaxation through muscarinic or alpha-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 M(1), M(2), and M(3) receptor subtypes, measured from affinity (pA(2)) values, was p-fluorohexahydrosiladifenidol (pFHHSiD) (M(3)) > pirenzepine (M(1)) > methoctramine (M(2)), indicating a predominance of M(3) subtype. This order was unchanged with age. Contractions by muscarinic agonist methacholine (MCh) were diminished in aged rats, resulting in lower apparent affinity (pD(2)) values, compared with adult controls. A larger decrease of MCh contractions occurred in aged rats after Ca(2+) 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.
Lopes
Guiomar Silva
GS
Department of Pharmacology, Federal University of São Paulo, São Paulo, Brazil. guiolopes@terra.com.br
Smaili
Soraya Soubhi
SS
Neto
Afonso Caricati
AC
Vladimirova
Irina
I
Jurkiewicz
Aron
A
Jurkiewicz
Neide Hyppolito
NH
D000322:Adrenergic Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D020013:Calcium Signaling / Q000502:physiology*; D003959:Diamines / Q000494:pharmacology; D017275:Isradipine / Q000494:pharmacology; D007583:Jejunum / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010528:Peristalsis / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D000322:Adrenergic Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003959:Diamines; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; C058297:4-fluorohexahydrosiladifenidol; D010890:Pirenzepine; C054938:methoctramine; D017275:Isradipine