Histamine-induced hydrolysis of polyphosphoinositides in guinea-pig ileum and brain

Eur J Pharmacol. 1986 May 27;124(3):255-65. doi: 10.1016/0014-2999(86)90226-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Chemistry / drug effects*
  • Female
  • Guinea Pigs
  • Histamine / pharmacology*
  • Hydrolysis
  • Ileum / drug effects
  • Ileum / metabolism*
  • In Vitro Techniques
  • Inositol Phosphates / metabolism*
  • Male
  • Muscle, Smooth / metabolism
  • Pyrilamine / pharmacology
  • Stimulation, Chemical
  • Sugar Phosphates / metabolism*
  • Time Factors

Substances

  • Inositol Phosphates
  • Sugar Phosphates
  • Histamine
  • Pyrilamine