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.
Rappen-Cremer
E
E
Institute of Pharmacology, University of Düsseldorf, FRG.
Borchard
U
U
Hafner
D
D
Berger
F
F
D000818:Animals; D003331:Coronary Vessels / Q000032:analysis*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000032:analysis*; D010643:Phenoxybenzamine; D011725:Pyridines / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000032:analysis* / Q000187:drug effects; D013552:Swine; D014132:Trachea / Q000032:analysis*
D011725:Pyridines; D011969:Receptors, Histamine H1; D010643:Phenoxybenzamine; D006632:Histamine; C006183:2-(2-aminoethyl)pyridine