Long-term nicotine exposure causes increased concentrations of trypsinogens and amylase in pancreatic extracts in the rat.
To develop radioimmunoassays (RIAs) for rat trypsinogens 1 and 2 and to investigate the effect of nicotine exposure on concentration and production of pancreatic zymogens in the rat.


METHODS
Male Sprague-Dawley rats were supplied with either normal or nicotine-containing (0.77 mM) water for 28 days and were then killed. Rabbit antibodies for the activation peptides of trypsinogens 1 and 2 were obtained for use in the RIAs. Concentrations of the both trypsinogens in pancreatic extracts were measured by the RIAs after activation by enterokinase. DNA and amylase were measured using commercial kits. mRNA for trypsinogens 1 and 2, procolipase, and cholecystokinin receptor was measured by in situ hybridization.


RESULTS
The specificity of the RIA for the trypsinogen 1 activation peptide was satisfactory. The RIA for the trypsinogen 2 activation peptide showed a limited cross-reaction toward the synthetic trypsinogen 1 activation peptide, but the importance of this cross-reaction was moderate when investigated in samples of activated trypsinogens. Weight gain was reduced in nicotine-treated animals. Concentrations of amylase, trypsinogen 1, trypsinogen 2, and the ratio of trypsinogen 2 to 1 were all increased in pancreatic extracts of nicotine-fed animals. Total DNA and mRNA for the trypsinogens, procolipase, and cholecystokinin receptor were not affected by nicotine exposure.


CONCLUSIONS
The combination of increased proenzyme concentrations and unaffected mRNA levels suggests that nicotine impairs secretion rather than production of pancreatic zymogens.
Lindkvist
Björn
B
Department of Clinical Sciences, Malmö University Hospital, Lund University, Malmö, Sweden. bjorn.lindkvist@vgregion.se
Wierup
Nils
N
Sundler
Frank
F
Borgström
Anders
A
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D003089:Colipases / Q000378:metabolism; D004765:Enteropeptidase / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D009842:Oligopeptides / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012815:Signal Processing, Computer-Assisted; D013997:Time Factors; D014362:Trypsinogen / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D003089:Colipases; D004792:Enzyme Precursors; D018722:Nicotinic Agonists; D009842:Oligopeptides; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; C080396:trypsinogen activation peptide; D009538:Nicotine; C037107:procolipase; D014362:Trypsinogen; D000681:Amylases; D004765:Enteropeptidase