H1-receptor reserves in guinea-pig left atria, trachea and pig coronary artery as identified by phenoxybenzamine.

H1-receptor reserves in guinea-pig left atria, trachea and pig coronary arteries were calculated by the use of phenoxybenzamine (Pba), a beta-haloalkylamine that irreversibly blocks the H1-receptor response to histamine or 2-(2-pyridyl)-ethylamine (PEA). Equieffective concentrations of the H1-agonist in the absence (A) and presence (A') of Pba were evaluated from concentration-response curves. By plotting the reciprocal values 1/A versus 1/A' the amount of H1-receptors not occupied by the agonist was calculated. The size of the H1-receptor reserve could be estimated by comparison of the receptor occupation with the corresponding effect. Furthermore, the dissociation constants for histamine, PEA, Pba and the pD'2-values for Pba were determined for the different tissues. 5% and 6% H1-receptor occupation is necessary to achieve a half maximal contraction of the trachea with the agonists histamine and PEA, respectively. Only 0.5% H1-receptor occupation is needed for the half maximal positive inotropic effect of histamine in left atria, while 5.5% of the H1-receptors have to be occupied using PEA as an agonist in this tissue. In the coronary artery of the pig 50% of the maximal contraction can be achieved by stimulation of 15.1% of the H1-receptors with histamine.