Dopamine, noradrenaline and isoprenaline: secretory and electrophysiological effects in vitro on mouse pancreas.

Abstract

SUMMARY1. The amylase release from mouse pancreatic fragments was studied after dopamine (DA), and a-or f-sympathomimetic agonist application. The electrical parameters of the acinar cell membrane were also monitored.2. Both DA (from 5 x 10-6 to 10-4 M) and f-stimulants (isoprenaline from 5 x 10-6 to 5 x 1O-5 M; noradrenaline from 3 x 10-4 to 10-3 M) evoked an increase in amylase release, while noradrenaline in a-receptor stimulating doses failed to have any effect.3. The stimulatory effect of DA was blocked by ganglion blockers (Arfonad 10-5 M; pentamethonium 3 x 10-5 M) in a competitive manner and a dual antagonism was observed with atropine (10-7 M, 10-9 M). An a-receptor antagonist (phentolamine 1O-5 M) and a fl-receptor antagonist (propranolol 10-5 M) had no influence on the dopamine response. Moreover, the DA-induced stimulation was dependent on the presence of extracellular calcium. Perfusion with 10-4 and 10-3 M-DA or local application (from 77 /ug to 4-3 mg), resulted in marked membrane depolarization with diminution of the input resistance. This effect was blocked by atropine (10-5 M) and pentamethonium (10-4 M), but not by propranolol (10-5 M) or phentolamine (10-5 M).4. The isoprenaline-(IP) and noradrenaline-(NA) induced increase in amylase release was competitively blocked by propranolol (10-5 M) but not by phentolamine (10-5 M). Atropine caused a dose-dependent (10-7 M, 10-6 M) decrease in the maximal response (non-competitive antagonism), while the ganglion blocker pentamethonium (10-4 M) was without effect.5. NA caused membrane depolarization accompanied by a decrease in the input resistance after local application (from 77 jug to 1-6 mg). This effect persisted in the presence of 10-5 M-phentolamine but was abolished by 10-5 M-propranolol. IP perfusion (10-4 and 10-3 M) or local application (0 3 M; from 32 to 130 jug) caused the same electrical changes as those induced by NA and DA. The effect of IP persisted in the presence of 10-5 M-phentolamine, 10-4 M-pentamethonium and 10-4 Mdomperidone, but was abolished by propranolol (10-5 M) and tetrodotoxin (5 X 10-6 M) and markedly diminished by atropine (10-5 M). 6. The unstimulated amylase release from mouse pancreatic fragments was diminished in the presence of atropine (up to 40 % of the resting secretion) and ganglion blockers, but did not change significantly in the presence of either a-or fl-antagonists.Z. BERGER AND R. LAUGIER 7. It is concluded that: (a) the basal amylase release of this preparation is mainly regulated by cholinergic mechanisms, i.e. spontaneous acetylcholine liberation from nerve endings influenced by intrapancreatic ganglia. (b) DA and f-stimulants acting on their specific receptors induce an increase in pancreatic acinar cell membrane permeability. On the basis of competitive antagonism between DA and ganglion blockers, and dual antagonism between DA and atropine, the DA receptor is probably located before (or on) the intrapancreatic ganglion and connected to a post-ganglionic cholinergic fibre. The tetrodotoxin inhibition...