Does the guinea-pig ileum obey the 'law of the intestine'?

1. We report the first simultaneous mechanical reflex responses of the long itudinal muscle (LM) and circular muscle (CM) layers of the guinea-pig ileu m following mucosal stimulation and distension in vitro. 2. Dissection techniques were used to prevent mechanical interaction betwee n the LM and CM layers both oral and anal to a stimulus site. 3. All graded stimuli produced graded contractions of both the LM and CM or ally and anally to the stimulus. Contractions occurred synchronously in the LM and CM and under no circumstances were inhibitory responses recorded in either muscle layer, despite the presence of ongoing cholinergic tone in b oth the LM and CM, Contractions were abolished by tetrodotoxin (1.6 mu M). 4. Local brush stroking of the mucosa evoked a peristaltic wave which readi ly conducted distally over 13 cm, without the presence of fluid in the lume n. No descending relaxation was observed. 5. Apamin (300 nM) disrupted evoked peristaltic waves and significantly inc reased the rate-of-rise of the LM and CBI contractions anal to a stimulus, and the LM oral to a stimulus. 6. N-omega-nitro-L-arginine (100 mu M), a. nitric oxide synthesis inhibitor , had no overall significant effect on the characteristics of the LM and CN contractions, although on occasion an enhancement in their peak amplitude was noted. 7. It is suggested that the guinea-pig ileum does not conform to the 'law o f the intestine' as postulated by Bayliss & Starling (1899). Rather, local physiological stimulation of the ileum elicits a contraction both orally an d anally to a stimulus, which occurs synchronously in both the Chi and LM l ayers. Apamin-sensitive inhibitory neurotransmission modulates the rate-of- rise of the anal contraction of the CM, possibly to generate distal propuls ion.