Histamine-induced hydrolysis of polyphosphoinositides in guinea-pig ileum and brain.
The effect of histamine and the H1-selective agonist, 2-pyridylethylamine, on the accumulation of inositol monophosphate (InsP), inositol bisphosphate (InsP2) and inositol trisphosphate (InsP3) has been examined in lithium-treated slices of guinea-pig cerebellum and ileal smooth muscle. Following 45 min incubation, histamine produced a large accumulation of [3H]InsP and a smaller accumulation of [3H]InsP2 and [3H]InsP3 in both tissues. In cerebellar slices all three responses to histamine were potently and competitively inhibited by the selective H1-receptor antagonist, mepyramine. In contrast, incubation of ileal slices with mepyramine (0.1 microM) produced only a small reduction (circa 20%) in the maximal accumulation elicited by histamine of each [3H]inositol phosphate with no significant effect on the EC50 or Hill coefficient. However, when 2-pyridylethylamine, instead of histamine, was used to stimulate inositol phospholipid hydrolysis in ileal smooth muscle, the agonist-induced responses appeared to be competitively antagonised by mepyramine. The results presented indicate that there is an apparent dissociation between histamine-induced InsP3 accumulation and H1-receptor-mediated contractile activity in ileal smooth muscle and suggest that agonist-induced inositol phospholipid hydrolysis in this tissue may be involved in other cellular events separate from those involving calcium.
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006868:Hydrolysis; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013403:Sugar Phosphates / Q000378:metabolism*; D013997:Time Factors
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D006632:Histamine; D011738:Pyrilamine