• 대한약리학회지
• /
• 제13권2호
• /
• pp.41-48
• /
• 1977

In 1968, Case et al. first studied the importance of cyclic AMP as an intermediate in the action of secretin and cholecystokinin-pancreozymin and they suggested that the action of secretin, not that of cholecystokinin-pancreozymin, may be mediated through cyclic AMP. Recently Albano et al. reported that in the exocrine pancreas each of the two major physiological functions is modulated a specific cyclic nucleotide, enzyme secretion by cyclic GMP, and fluid and ionic secretion by cyclic AMP. But in pancreas still conflicting results have been reported on the role of cyclic nucleotides in enzyme and electrolyte secretion. In these study, the role of cyclic nucleotides in the exocrine pancreatic secretion was examined. The results are as follows. 1) Very strong stimulation on amylase release from guinea pig pancreatic slice was produced by 1 unit of cholecystokinin-pancreozymin but as compared to that of cholecystokinin-pancreozymin very weak response was observed by 1 unit of secretion or $1\;{\mu}g$ of VIP. 2) Both cholecystokinin-pancreozymin and acetylcholine produced a rapid and marked rise in cyclic GMP as well as cyclic AMP in isolated pancreatic tissue. However, both secretin and VIP failed to alter significantly the basal level of cyclic GMP in pancreatic fragments. 3) Atropine inhibited acetylcholine mediated amylase release, but did not affect the cholecystokinin-pancreozymin response. Furthermore, atropine pretreatment produced a marked inhibitory effect on the increase of tissue cyclic nucleotides induced by cholecystokinin-pancreozymin and acetylcholine. In summary, these results suggest that whereas the pancreatic secretion produced by secretin and VIP is modulated by the formation of cyclic AMP, the pancreatic enzyme secretion in response to cholecystokinin-pancreozymin and acetylcholine is triggered by both cyclic AMP and cyclic GMP.

• Archives of Pharmacal Research
• /
• 제18권6호
• /
• pp.434-439
• /
• 1995

In pancreatic cells, NO formation is associated with increased levels of cGMP and endocrine/exocrine secretion. In the present study, the role of NO in the regulation of exocrine secretion was investigated in rat pancreatic tissues. Treatment of rat pancreatic tissue with sholecystokinin-pancreozymin (CCK-PZ) resulted in an significant increase in arginine conversion to citruline, the amount of nitrite/nitrate, the release of amylase, and the level of cGMP. Furthermore, CCK-PZ stimulated increase of amylase release and conversion of arginine to citrulline transformation were counteracted by the inhibitor of NO synthase, $N^G-nitro-L-arginine$ methyl ester. The results on the time course of CCK-PZ-induced citrulline formation within the first seconds of simulation. The kinetics of citrulline accumulation correlate well with those of cGMP rise, which further confirms the conclusion that NO mediates the response to CCK-PZ by cGMP.

• 대한약리학회지
• /
• 제16권1호
• /
• pp.35-39
• /
• 1980

In this study, the effects of phenoxybenzamine and related drugs on the action of CCK-PZ and caerulein were examined in isolated gall bladder of guinea pig and higher esophagus strip of fowl. The strips were placed in a bath containing Locke-Ringer solution maintained at $38^{\circ}C$. Oxygen was continuously bubbled through the solution. The contractile response was measured isometrically by a force displacement transducer connected to polygraph. In isolated gall bladder preparation caerulein produced contractile response of CCK-PZ type, but the relative potency on a weight basis was 30 times stronger than CCK-PZ. The response of caerulein or CCK-PZ was not blocked by cholinergic blocking agent and both alpha and beta adrenergic blockades, however, the response of caerulein or CCK-PZ was exceptionally blocked by phenoxybenzamine. In isolated esophagus strip CCK-PZ with high concentration produced marked contraction which was not modified by atropine and other blocking agents, whereas the response was blocked by phenoxybenzamine. These results lead to the conclusion that phenoxybenzamine inherently inhibits the contractile response of CCK-PZ and caerulein on esophagus and other smooth muscle.

• Archives of Pharmacal Research
• /
• 제19권3호
• /
• pp.201-206
• /
• 1996

Nitric oxide (NO) is thought to be a second messenger involved in secretion. Upon stimulating pancreatic acinar cells with cholecystokinin-pancreozymin (CCK-PZ), NO formation has been shown to be associated with increased levels of cGMP (Seo et al., 1995). To elucidate the signaling pathway of VIP-induced enzyme secretion, we investigated the NO and cGMP synthesis steps as potential steps where two signal pathways triggered by CCK-PZ and VIP interact. The results obtained in this work provide evidence that increase in pancreatic enzyme secretion by treatment with VIP has no relationship with NOS activity and cGMP level. This conclusion was derived from the following findings that VIP treatment of rat pancreatic tissue increased amylase release as well as protein output in a dose- and time-dependent manner, whereas NOS activity and cGMP synthesis were not affected by VIP treatment as monitored by NOS activity assay and determining cGMP level, which was further confirmed by a NOS-inhibitor study. Consequently, CCK-PZ or VIP increases enzyme secretion in rat pancreatic tissue, but the two hormones are different in their mode of action. Together the results suggest that signaling pathway of VIP-induced enzyme secretion might either bypass the NO and cGMP synthesis steps or lie on a distinct pathway from CCK-PZ-induced pathway.