Substance P stimulates sphincter of Oddi motility and inhibits trans‐sphincteric flow in the Australian brush‐tailed possum

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Abstract
Substance P containing nerves are widely distributed throughout the gastrointestinal tract. The aims of this study were to determine the distribution of substance P containing nerves in the extrahepatic biliary tree of the Australian brush‐tailed possum and to characterize the effect of exogenous substance P on the sphincter of Oddi (SO) motility and trans‐sphincteric flow in vivo. Immunohistochemical staining of fixed specimens (n = 8) found moderate numbers of substance P containing nerve cell bodies and fibres throughout the neural plexuses of the SO, in particular in the serosal and intraluminal nerve trunks of the SO and gallbladder. Synthetic porcine substance P (1–2000 ng kg−1), administered by close intra‐arterial injection (i.a. n = 7), produced a dose‐dependent elevation in basal pressure [P < 0.01] and an associated dose‐dependent reduction in trans‐sphincteric flow [P < 0.0001]. Substance P had no significant dose‐dependent effect on SO phasic contraction amplitude or frequency. Tetrodotoxin (9 μg kg−1, i.a.) did not inhibit the effect of substance P on SO motility and trans‐sphincteric flow (n = 5). In conclusion, substance P containing nerves are found throughout the possum extrahepatic biliary tree. Exogenous substance P stimulates SO motility and reduces trans‐sphincteric flow in vivo by acting directly on the sphincter smooth muscle.