H₁ Receptor Mediates Inositol Phosphates Response to Histamine in Gastric Smooth Muscle of Guinea Pigs

Abstract

The effect of histamine on [³H]-inositol phosphates (IPs) formation was investigated with [³H]-inositol-labeled gastric smooth-muscle cells in guinea pigs. Histamine (10⁻⁵ M) increased the formation of [³H]-IPs in the muscle cells. The increase was significantly inhibited by pyrilamine (10⁻⁵ M) but not by cimetidine (10⁻⁵ M). The contractile response to histamine was also completely inhibited by pyrilamine but not by cimetidine. Phorbol ester 12-myristate 13-acetate (10 μM) significantly inhibited histamine-stimulated [³H]-IPs formation by 56%, whereas forskolin (10 μM) decreased it by 18%. This study demonstrates that the response of [³H]-IPs formation and contraction to histamine is mediated through H₁ receptor, and the formation of [³H]-IPs is negatively regulated by protein kinase C in gastric smooth muscle of guinea pigs.

Key Words:

• Histamine
• inositol phosphates
• smooth-muscle contraction