Different mechanisms are responsible for the contractile effects of histaminergic compounds on isolated intestinal smooth muscle cells.
The effects of histamine and dimaprit on intestinal smooth muscle contractility were investigated on isolated cells from longitudinal muscle of the guinea pig ileum. Both histamine (10(-14)-10(-10) M) and dimaprit (10(-13)-10(-10) M) exerted a concentration-dependent contraction of intestinal cells, causing a maximum decrease in cell length of about 20%. This effect was not significantly different from that induced by cholecystokinin-octapeptide (CCK-8) 10(-9) M. The concentration-response curves to histamine and dimaprit were shifted to the left in the presence of the histamine H2-receptor antagonist famotidine (10(-7) M) indicating the occurrence in the smooth muscle of H2 receptors mediating relaxation. Whereas the contraction produced by histamine was competitively antagonized by the H1 receptor antagonist mepyramine (10(-8) M), neither mepyramine (10(-7) M) nor temelastine (10(-7) M) did modify the contractile effect of dimaprit. In contrast, atropine (10(-8) M) significantly depressed the maximum response to dimaprit without affecting that exerted by histamine. These data indicate that histamine and dimaprit can modify intestinal contractility, by acting via different mechanisms; while the contractile action of histamine is related to H1 receptor activation, that produced by dimaprit involves cholinergic pathways.
Bertaccini
G
G
University of Parma, Institute of Pharmacology, Italy.
Morini
G
G
Coruzzi
G
G
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D017259:Dimaprit / Q000494:pharmacology; D015738:Famotidine / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D017442:Histamine Agonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology
D017442:Histamine Agonists; D006635:Histamine H2 Antagonists; D018727:Muscarinic Antagonists; D015738:Famotidine; D001285:Atropine; D006632:Histamine; D012844:Sincalide; D017259:Dimaprit