On the secretagogue effect of dibutyryl cyclic AMP in the rat exocrine pancreas

Summary DbcAMP0.1 mM induces the discharge of exportable enzymes from rat pancreas fragments incubated in vitro. This effect is qualitatively similar to the action of physiological secretagogues acting via hormone receptors: 1) it is accompanied by the appearance of exocytotic images at the acinar cell apex; 2) it is energy dependent but energy supply is low while that required for the carbamylcholine or caerulein response is high and can only be afforded by oxidative phosphorylation; 3) it is calcium dependent, but no alteration of inward or outward calcium movement can be observed; 4) it is altered by agents known to disrupt the microfilamentous microtubular system [41]. However, the secretory response to DbcAMP is quantitatively less than that obtained with hormonal stimuli. A damaging effect of DbcAMP on pancreatic acinar cells is ruled out on histological and biochemical grounds: there is no significant leakage of LDH; protein synthesis, 2-deoxy-d-glucose andl-leucine uptake are unaltered. The secretagogue effect of DbcAMP is reversible, dose-related and specific. It is not mediated by neuro-transmitter release or by interaction with their receptors. The evidence presented points to a direct interaction of DbcAMP on the pancreatic acinar cell and suggests the last step of the secretory cycle as the most probable site of action of the nucleotide derivative.Abbreviations cAMP Adenosine-3,5-monophosphate - cyclic DbcAMP: N⁶-2-O-Dibutyryl-adenosine-3,5-monophosphate, cyclic - DbcGMP N²-2-O-Dibutyryl-guanosine-3,5-monophosphate, cyclic - 5-AMP Adenosine-5-monophosphate - TCA Trichloracetic acid - ATP Adenosine triphosphate - NADH Nicotinamide-adenine dinucleotide - Tris Tris-(hydroxy-methyl) amino-methane - EGTA Ethylene glycol-bis ( aminoethylether)-NN-tetraacetic acid - LDH Lactic dehydrogenasePart of this work has been presented in abstract from at the VIIIth Symposium of the European Pancreatic Club, Toulouse, France, October, 1975, 23rd–25th and at the Biochemical Society of Belgium [40]This work was partially carried out under contracts from the Ministère de la Politique Scientifique within the framework of the Association Euratom—University of Brussels—University of Pisa, and the Institut National de la Santé et de la Recherche Médicale (France)