Release of digestive enzymes from isolated rat pancreatic acini following muscarinic stimulation: a comparative study with enzyme release and receptor binding.
Effect of cholinergic stimulation on the release of digestive enzymes from isolated rat pancreatic acini prepared by collagenase digestion was investigated. The release of enzymes (amylase, chymotrypsinogen, lipase) increased linearly with the time of incubation in the absence of secretagogues. Carbachol, a muscarinic agonist, induced a remarkable increase in the release of these enzymes. This carbachol-stimulated amylase release showed a biphasic curve, and its maximal response was observed at 10(-5) M. The release patterns of chymotrypsinogen and lipase were similar to that of amylase. This carbachol-stimulated amylase release was inhibited by atropine in a dose-dependent manner, with an ED50 value of 1.17 X 10(-8) M. Other cholinergic agonists such as methacholine also stimulated the release of these enzymes, and these increases in the release were inhibited by atropine. Scatchard analysis for [3H]quinuclidinyl benzilate ([3H]QNB) binding to isolated pancreatic acini revealed that the binding site of [3H]QNB was a single component with a Kd value of 0.09 nM and a Bmax value of 89.3 fmol/mg protein, respectively. The effect of other cholinergic antagonists, pirenzepine and AF-DX 116 (11-[[2-[(diethylamino) methyl]1-piperidinyl]acetyl]-5,11-dihydro- 6H-pyrido[2,3-b][1,4]-benzodiazepine-6-one), on pancreatic acini was also investigated. Based on these results, it has been concluded that isolated rat pancreatic acini have muscarinic receptors and are useful for analyzing the mechanism of pancreatic enzyme secretion.
Kato
M
M
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
Ohkuma
S
S
Kataoka
K
K
Kashima
K
K
Mukainaka
T
T
Kuriyama
K
K
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002919:Chymotrypsinogen / Q000378:metabolism*; D066298:In Vitro Techniques; D008049:Lipase / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000201:enzymology*; D010277:Parasympathomimetics / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D002217:Carbachol; D002919:Chymotrypsinogen; D008049:Lipase; D000681:Amylases