Responses to histamine and selective H2-receptor agonists in lung parenchymal strips from normal and sensitized guinea-pigs.
Histamine produces concentration-dependent contractions of lung parenchyma strips obtained from normal and sensitized guinea-pigs. The responsiveness of the sensitized lung strips to histamine was significantly increased compared to normal tissues. Clemizole (0.1 microM) was equally effective as an H1-antagonist in normal (dose-ratio 9.12) and sensitized (dose-ratio 9.77) tissues. The concentration-response curves to histamine were displaced to the left by cimetidine (0.1 microM to 0.1 mM) with similar dose-ratios in normal and sensitized tissues. Cimetidine enhanced maximal responses to histamine only in normal lung strips. The effects of submaximal equieffective concentrations of histamine were augmented to the same extent by cimetidine (0.1 mM) in normal and sensitized tissues. The responses to histamine were not modified by indomethacin (5 microM). The responsiveness and sensitivity of sensitized lung strips to isoprenaline, impromidine, 4-methyl-histamine and dimaprit were not different from those of normal tissues. Cimetidine yielded, as antagonist of dimaprit, similar pA2 values in normal and sensitized tissues. In conclusion, there is no experimental evidence in favour of the existence of an impairment of H2-receptor activity in sensitized airways. Hyperreactivity to histamine is probably due to differences between normal and sensitized tissues with respect to Ca2+ entry and/or intracellular Ca2+ release in response to H1-receptor activation.
Cortijo
J
J
Departamento de Farmacología y Farmacotecnia, Universitat de València, Spain.
Sanz
C
C
Perpiñá
M
M
Ortiz
J L
JL
Orón
J D
JD
Esplugues
J
J
Morcillo
E J
EJ
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D017446:Impromidine; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000187:drug effects* / Q000502:physiology; D013890:Thiourea / Q000494:pharmacology
D001562:Benzimidazoles; D006146:Guanidines; D007093:Imidazoles; D008761:Methylhistamines; D011970:Receptors, Histamine H2; C025566:4-methylhistamine; D002927:Cimetidine; D006632:Histamine; D017446:Impromidine; D013890:Thiourea; D007545:Isoproterenol; D017259:Dimaprit