A study of the histamine H₂‐receptor mediating relaxation of the parenchymal lung strip preparation of the guinea‐pig

Abstract

The relaxation produced by several H2-receptor agonists and forskolin was investigated on strips of guinea-pig lung parenchyma. Dimparit, 1 microM to 10 mM, 4-methyl histamine, 0.5 microM to 100 microM and impromidine, 10 nM to 1 microM, had no effect on the tone of the unstimulated strips of lung parenchyma but caused a dose-dependent relaxation of strips that were contracted by 2-pyridylethylamine (2-PEA), 15 microM. Forskolin, 10 nM to 4 microM, produced a dose-dependent relaxation of both the stimulated and unstimulated lung strips. The muscarinic antagonist atropine, 1 microM, and the beta 2-adrenoceptor antagonist propranolol, 10 microM, had no effect on the dose-response curve for dimaprit-induced relaxation of the lung strip. The dose-response curve for dimaprit was shifted to the right in a dose-dependent manner by increasing concentrations of a variety of H2-antagonists. Schild plots produced a straight line for all the H2-antagonists with slopes not significantly different from unity. The equilibrium dissociation constants for the H2-antagonists on the lung strip preparation were similar to those previously reported for inhibition of the chronotropic activity of histamine on guinea-pig right atria and inhibition of [3H]-tiotidine binding to homogenates of guinea-pig lung parenchyma.

The binding of [3H]‐tiotidine to homogenates of guinea‐pig lung parenchyma

“…Ranitidine has previously been shown to be 4 to 10 times more potent than cimetidine at the H2-receptor (Bradshaw et al, 1979) but the lung and cerebral cortex studies shown in Table 2 In conjunction with the preceding paper (Foreman et al, 1985) we have demonstrated an H2-receptor by binding studies whose interaction with agonists and antagonists quantitatively matches the pharmacological potencies of these drugs on the contractile responses of the lung strip.…”

“…We have compared the inhibition constants obained in this study for a variety of H2-compounds, with KB values calculated from inhibition of the action of dimaprit in lung parenchyma reported in the preceding paper (Foreman et al, 1985) and from the inhibition of the chronotropic activity of histamine in guinea-pig right atria (Table 2). For the H2-antagonists there is a correlation between the inhibition constants obtained in the present study and the dissociation constants obtained in both the isolated lung strip and the right atria (r = 0.97, P < 0.01 and r = 0.95, P < 0.01 respectively).…”

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…Whereas early studies in guinea pig brain, lung, and transfected CHO cells have been successful using [ 3 H]tiotidine (cf. 31) (Gajtkowski et al, 1983;Norris et al, 1984;Foreman et al, 1985;Gantz et al, 1991b), studies in rat brain and guinea pig mucosal cells were not successful (Maayani et al, 1982;Batzri and Harmon, 1986). The introduction of […”

Characterization of the histamine receptors in the guinea‐pig lung: evidence for relaxant histamine H3 receptors in the trachea

“…H1 receptors are coupled to inositol phosphate hydrolysis and mediate a variety of responses, including smooth muscle contraction, increased vascular permeability and hormone release (Hill, 1990). H2-receptors are coupled to adenylate cyclase via a G.-protein and the functional H2-responses include smooth muscle relaxation and inhibition of the immune system (Foreman et al, 1985). H3-receptors were originally recognized in rat brain where they appeared to be involved in the feedback control of both histamine synthesis and release (Arrang et al, 1987).…”