Further investigations on the antipropulsive effect of centrally administered histamine and its relation with morphine.
The effect of intracerebroventricularly (i.c.v.) administered histamine (100 micrograms/rat) on intestinal myoelectrical activity was investigated in the jejunum of fasted rats. Histamine caused the disappearance of phase III and a partial reduction of phase II of migrating myoelectric complexes. This effect was antagonized by i.c.v. pretreatment with mepyramine (10 micrograms/rat), an H1 receptor antagonist. Lesions of central noradrenergic neurons by i.c.v. injection of the neurotoxin 6-hydroxydopamine strongly reduced both the inhibition of intestinal propulsion and the migrating myoelectric complexes profile induced by i.c.v. histamine, whereas pretreatment with p-chlorophenylalanine, a selective depletor of serotonin stores, had no effect. It thus appears that aminergic pathways are involved in the visceral effects of central histamine. Mepyramine (200 micrograms/rat i.c.v.) partially reduced the slowing of intestinal transit induced by high doses of morphine. Pretreatment with compound 48/80 (10 micrograms/rat i.c.v.), a mast cell degranulator, but not with alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, reduced the antipropulsive action of i.c.v. morphine to the same extent as mepyramine, suggesting that histamine released from cerebral mast cells by high doses of morphine could contribute to the intestinal inhibition by morphine.
Patrini
G
G
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Massi
P
P
Rubino
T
T
Donin
L
L
Gori
E
E
Parolaro
D
D
D000818:Animals; D005215:Fasting; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007583:Jejunum / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D012701:Serotonin; D009020:Morphine; D006632:Histamine; D016627:Oxidopamine; D011738:Pyrilamine; D009638:Norepinephrine