Excitatory motor innervation in the canine rectoanal region: role of changing receptor populations.

1. Motor innervation in the canine rectoanal region was examined in isolated strips of the circular muscle layer. Contractile responses to electrical field stimulation began at lower frequencies and were more persistent in the internal anal sphincter (IAS) than in the rectum. 2. Motor innervation to the IAS was almost exclusively sympathetic, since it was blocked by guanethidine (Guan 3 microM) while the response in the proximal rectum was approximately 50% muscarinic, and sensitive to the M(3) selective antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, 0.1 microM) and 50% tachykinergic, and sensitive to the neurokinin 2 (NK(2)) receptor antagonist GR 94800 (1 microM). From IAS to rectum there was a gradual shift in the relative contribution of intrinsic and extrinsic neural innervation. 3. Responses to exogenously applied transmitters exhibited a similar pattern to that observed with motor innervation. Norepinephrine (NE) was most potent in the IAS and acetylcholine (ACh) and NK-A were most potent in the proximal rectum. The responses were inhibited by prazosin, 4-DAMP and GR 94800 respectively. 4. A gradient in the density of adrenergic alpha(1), muscarinic and NK(2) receptors also existed from IAS to rectum as determined by measuring the binding of [(3)H]-prazosin, [(3)H]-quinuclidinyl benzilate ([(3)H]-QNB and [(3)H]-SR-48968 to smooth muscle membranes. 5. In summary, these data suggest that the shift in motor innervation in the rectoanal region is achieved in part by changes in receptor populations available for activation by sympathetic and enteric motor neurons.