Chronic denervation of rat jejunum results in cholinergic supersensitivity due to reduction of cholinesterase activity.
We examined the effects of chronic myenteric/extrinsic denervation of a segment of rat small intestine on specific acetylcholinesterase (AChE) and nonspecific cholinesterase (ChE) activities. Myenteric/extrinsic denervation of a 5-cm length of jejunum was accomplished by serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride. Fifteen days after denervation, biochemical determinations of AChE and ChE revealed that the smooth muscle layers, but not the mucosa, of denervated tissues have decreased levels of both AChE (approximately 65% decreased) and ChE (approximately 30% decreased). Histochemical staining of sections of denervated small intestine for AChE activity failed to detect any AChE activity in the region formerly occupied by the myenteric plexus. There appeared to be a qualitative decrease in ChE staining in the longitudinal muscle of denervated small intestine. Isolated muscle contraction experiments were conducted with the aim of determining changes in muscle responsiveness to acetylcholine (ACh) subsequent to denervation. Denervated circular and longitudinal muscle layers displayed increased sensitivity to ACh compared to nondenervated tissues (pEC50 values: 5.23 vs. 3.53, circular muscle; 5.33 vs. 4.08, longitudinal muscle). Incubation of tissues with 10 microM neostigmine caused a similar shift in pEC50 values of ACh concentration-response curves from denervated circular and longitudinal muscle layers (approximately 20% increase in pEC50). In contrast to the similar effects of neostigmine on both muscle layers of denervated tissues, neostigmine exerted a differential effect on the muscle layers of control intestine. Neostigmine produced a 65% increase in pEC50 value in control circular muscle and a 49% increase in pEC50 value in control longitudinal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
School of Pharmacy, University of Wisconsin-Madison.
M A
MA
Osinski
P
P
Bass
D000109:Acetylcholine / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002799:Cholinergic Fibers / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D002802:Cholinesterases / Q000378:metabolism*; D004347:Drug Interactions; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000201:enzymology; D007583:Jejunum / Q000187:drug effects / Q000201:enzymology* / Q000294:innervation*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009121:Muscle Denervation; D009130:Muscle, Smooth / Q000201:enzymology; D009388:Neostigmine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013563:Sympathectomy, Chemical
D009388:Neostigmine; D000110:Acetylcholinesterase; D002802:Cholinesterases; D000109:Acetylcholine