Histamine as a central modulator of rat intestinal transit.
Histamine (HA) injected i.c.v. to rats inhibited intestinal propulsion in linear relation to the log of the administered doses (in the range from 20-100 micrograms/rat). In the same dose range HA also induced a dose-related analgesic effect (tail-flick test). The dose of HA maximally active by the i.c.v. route (100 micrograms/rat) showed neither of these effects when injected i.v. or i.p. HA-induced intestinal inhibition and analgesia were antagonized competitively by i.c.v. mepyramine (10 micrograms/rat), an H1 receptor antagonist, whereas cimetidine (10 micrograms/rat), an H2 receptor antagonist, had no effect. Repeated i.c.v. injections of HA resulted in tachyphylaxis of both intestinal inhibition and analgesia. Pretreatment with i.c.v. naloxone (20 micrograms/rat) antagonized the antipropulsive effect of HA in a noncompetitive fashion, but did not affect its antinociceptive action. The relevance of the central histaminergic system in the modulation of gastrointestinal motility and its relationship with the opioid system are discussed.
Parolaro
D
D
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Patrini
G
G
Massi
P
P
Mainardi
P
P
Giagnoni
G
G
Sala
M
M
Gori
E
E
D000698:Analgesia; D000818:Animals; D001921:Brain / Q000187:drug effects*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D006634:Histamine H1 Antagonists; D009270:Naloxone; D006632:Histamine