Studies on the nervous influence of external pancreatic secretion
In early Pavlov(1888, 1893) demonstrated that stimulation of the peripheral ends of vagus nerve caused the pancreas to secrete in unanesthetized animals but failed to obtain similar results in acute experiments. Pavlov interpreted that the vagi convey two kinds of fibers to the pancreas, excitatory and inhibitory, However, von Anrep(1914) was unable to prove Pavlov's concept with regard to the separate secretory and inhibitory branches of the vagi. Nevertheless he claimed that during the inhibitory phase the juice was secreted but retained in the gland owing to
contraction of the ducts. This hypothesis was later confirmed by Korovitsky(1923) that stimulation of the vagi causes contraction of the larger ducts.
Furthermore, cutting the extrinsic nerves has surprisingly little effect on pancreatic function. No observable loss of function results from division of the vagi or splanchnic nerves. Thomas(1950) proposed that local reflex mechanism rather than extrinsic innervation may concern to pancreatic function. Thomas considered,
the local reflex paths probably consists of connections between the intrinsic ganglia of the pancreas and the enteric nerve plexus. However, the importance of nerves has subsequently been minimized with regard to volume regulation by the discovery of the hormone secretin in 1902 and to enzyme regulation by the discovery of the hormone pancreozymin in 1943. Yet it is certain that nerves do play some part, particularly, it is evident by the recent work of White, Lundh and Magee(1960) that gastric distension increased pancreatic secretion when the vagi are intact.
In this regard parasympathomimetic agents, which of course mimic the effect of vagal stimulation increase enzyme content of the juice produced by the pancreas.
Atropine will abolish the response to pilocarpine. In unanesthetized animals there is abundant evidence that atropine depress the volume and enzyme response of the pancreas not only to stimulants acting within the gastrointestinal tract, but also
to parenterally administered secretin(Thomas and Crider, 1946). Nevertheless in effective doses atropine caused so much central excitation that is was difficult to determine whether the effects on pancreatic secretion were due to autonomic blockade or to central excitment. On the other hand in anesthetized animals, there is little evidence that atropine has any significant effect on the response to exogenous secretin or pancreozymin. Moreover, several investigators have noted a secretagogue action of atropine on the pancreas when the agent is given in massive
doses(10-80mg/kg). Recently Hong et al.(1961) found that a ganglionic blocking agent hexamethonium abolished the volume and enzyme response of human pancreas to oral milk or amino acid. Magee and his co-workers(1963) also found that ganglionic blocking agents as well as acute vagotomy and stropine decreased the response of the pancreas to intravenous secretin as compared with untreated controls with intact vagi of concious animals. After vagotomy they noticed the drugs had no further effect.
In order to assess the role of innervation in the regulation of digestive secretion of the pancreas we have studied the effects of pancreozymin and a member of pharmacological stimulating or blocking agents on the pancreatic secretion in the presence of a secretion background in anesthetized dogs.
Dogs between 8 and 14kg were anesthetized with chloralose, approximately 60mg/kg in propylene glycol after prime thiopental anesthesia(20mg/kg). The abdominal cavity was opened, the main pancreatic duct cannulated and the accessory duct ligated. A tube inserted into stomach for drain of gastric juice or the pylorus was ligated. All agents were injected intravenously through the polyethylene tube put in femoral vein.
Secretin(Jorpes and Mutt preparation) was infused throughout the experiment.
Other agents used are as follows: pancreozymin, pilocarpine nitrate, dimethylphenylpiperazine iodide(DMPP), atropine sulfate, scoploamine hydrobromide and hexamethonium chloride. Pancreatic juice in the presence of a secretin background was collected since there is very little flow of pancreatic juice in the fasted anesthetized dog. The pancreatic amylase, lipase and trypsin were measured by the methods previonsly described(Hong, 1967)
Summary and Conclusion
In anesthetized dogs the nervous influence to external pancreatic secretion particularly on enzyme output was investigated with a member of pharmacological stimulating or blocking agents and obtained the following results.
1) The volume response to continuous secretin infusion occurred in a steady state and secretory rate was increased by the raising dose in a limited range. Pancreozymin brought about a marked increase in enzyme output.
2) A parasympathomimetic agent pilocarpine and a ganglionic stimulant DMPP exert an increase of pancreatic enzyme content in secretin juice, however these agents were less effective in the enzyme increase than pancreozymin. The volume response to DMPP was depressed but the response to pilocarpine was enhanced.
3) The anticholinergic agent atropine was found to decrease the secretory response of pancreas only in a moderate dose(1.0mg/kg). Larger dose of atropine increased enzyme output particularly in trypsin.
4) Scopolamine did not depress the secretory response of pancreas but increased by increasing doses.
5) A ganglionic blocking agent hexamethonium decreased the response of pancreatic secretion to secretin.
By the above results it is concluded that both the vagi and local reflex influences to external pancreatic function measuring by pharmacologic agents were not important in anesthetized dogs, however, the fact that atropine in moderate dose or ganglionic blockade in a small dose depressed somewhat the secretory
response of pancreas to secretin supports that the nervous component may affect in the release of hormones or in the sensitivity of the gland to hormones.