Regional differences in cholinergic innervation and drug sensitivity in the smooth muscles of pig stomach

1 To evaluate the regional differences in cholinergic mechanisms in the stomach, innervation and receptor distribution were investigated by isometric tension recording, receptor binding assay and measurement of nerve-related enzyme activity in longitudinal and circular smooth muscle layers isolated from various regions of the pig stomach. 2 The response to transmural nerve stimulation (TMS) varied with the muscle layer and portion of stomach tested. Contraction was predominant in the smooth muscle from the pyloric antrum, relaxation in the corpus region. 3 The contraction to TMS was abolished by atropine (0.1-0.5 microM) and potentiated by physostigmine (1-2 microM). On the other hand, relaxation to TMS was unaffected by a combination of phentolamine and carteolol but was abolished by tetrodotoxin (TTX) (0.67-1.54 microM). In all preparations from various portions, physostigmine unmasked the contraction and atropine revealed the relaxation to TMS. 4 The activity of choline acetyltransferase (ChAT) and cholinesterase (ChE) was higher in longitudinal than in circular muscle layers and was also higher in the fundus than in any other portion. 5 The sensitivity (pD2 value) to acetylcholine (ACh) was higher in the longitudinal than in the circular muscle layers but did not differ largely among different regions of the stomach. The maximum response induced by ACh was also highest in longitudinal muscle of the fundus. In contrast, the population of muscarinic receptors, estimated from [3H]-QNB binding, increased from the fundic to pyloric portions. 6 These results suggest that there are regional differences in the responses to nerve stimulation in pig stomach, which are likely to depend partly on the quantitative differences in cholinergic nerve supply and in the responsiveness to ACh.