Dopamine, noradrenaline and isoprenaline: secretory and electrophysiological effects in vitro on mouse pancreas.
The amylase release from mouse pancreatic fragments was studied after dopamine (DA), and alpha- or beta-sympathomimetic agonist application. The electrical parameters of the acinar cell membrane were also monitored. Both DA (from 5 X 10(-6) to 10(-4) M) and beta-stimulants (isoprenaline from 5 X 10(-6) to 5 X 10(-5) M; noradrenaline from 3 X 10(-4) to 10(-3) M) evoked an increase in amylase release, while noradrenaline in alpha-receptor stimulating doses failed to have any effect. 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 alpha-receptor antagonist (phentolamine 10(-5) M) and a beta-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 micrograms 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). 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. NA caused membrane depolarization accompanied by a decrease in the input resistance after local application (from 77 micrograms 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 micrograms) 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) M-domperidone, but was abolished by propranolol (10(-5) M) and tetrodotoxin (5 X 10(-6) M) and markedly diminished by atropine (10(-5) M).(ABSTRACT TRUNCATED AT 400 WORDS)
D000200:Action Potentials / Q000187:drug effects; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D008725:Bis-Trimethylammonium Compounds / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005730:Ganglionic Blockers / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000494:pharmacology*; D010179:Pancreas / Q000502:physiology*; D013268:Stimulation, Chemical; D013565:Sympatholytics / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D008725:Bis-Trimethylammonium Compounds; D005730:Ganglionic Blockers; D013565:Sympatholytics; D013779:Tetrodotoxin; C014147:pentamethonium; D004294:Domperidone; D001285:Atropine; D000681:Amylases; D007545:Isoproterenol; D004298:Dopamine; D009638:Norepinephrine