THE SOURCE AND ACTION OF HISTAMINE IN THE ISOLATED GUINEA-PIG GALLBLADDER

We have investigated the effects of histamine on motility of the gallb ladder and characterized the receptor types involved. Histamine and th e histamine H-1-receptor agonist, 2-thiazolylethylamine (2-TEA) contra cted the isolated guinea-pig gallbladder strip in a dose dependent man ner. The contractile response to histamine was shifted to the right by the H-1-receptor antagonist, mepyramine. In pre-contracted gallbladde r strips, the H-2-receptor agonist dimaprit reduced the tension genera ted in a dose dependent fashion. The histamine H-2-receptor antagonist , ranitidine shifted the histamine concentration effect curve to the l eft and attenuated the dose dependent relaxations elicited at high con centrations. The histamine H-3-receptor agonist, (R)-alpha-methylhista mine (RMHA) elicited dose dependent contraction of the tissue which wa s significantly inhibited in the presence of mepyramine. The effects o f electrical field stimulation (EFS) on the strips were not significan tly altered by the presence of RMHA (10(-10)-10(-7) M) indicating litt le pre-synaptic H-3 activity in this tissue. Histamine immunoreactivit y (IR) was detected in gallbladder whole mount preparations of the muc osa and the muscularis/serosa. The histamine IR appeared cell bound in cells of varying morphological characteristics but no IR was detected in nerve fibres or cell bodies (ganglia). Alcian blue staining was co nsistent with the distribution of histamine IR cells as mast cells. Th e results indicate that histamine is distributed in the guinea-pig gal lbladder and it can regulate contractile activity via activation of H- 1 and H-2 but not H-3 receptors.