European Journal of Pharmacology, 55 (1979) 337--339 © Elsevier/North-Holland Biomedical Press
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Rapid communication IN VITRO A N A P H Y L A X I S IN GUINEA-PIG LUNG: EVIDENCE F O R THE PROTECTIVE R O L E OF HISTAMINE H2-RECEPTORS N. CHAND Ddpartement d'Anatomie et Physiologie animales, Facultd de Mddecine vdtdrinaire, Universitd de Montrdal, Saint-Hyacinthe, Qudbec, Canada J2S 7C6 Received 14 March 1979, accepted 20 March 1979
The H2-antagonist metiamide has been reported to potentiate in vitro allergic bronchoconstriction in man (Dunlop and Smith, 1977) and the in vivo pulmonary anaphylactic response in the guinea-pig (Drazen et al., 1978). The occurrence of H2-receptors mediating relaxation in the peripheral airway of guinea pig has been established (Chand and DeRoth, 1978}. We n o w demonstrate the protective role of H2-receptors in in vitro anaphylaxis (Schultz-Dale phenomenon) in the guinea-pig lung parenchymal strip (GPLS: peripheral airways: bronchiolar-alveolar ducts and alveoli, Lulich et al., 1976). Guinea-pigs (n = 39) of either sex, weighing 500--800 g were sensitized b y i.p. injection of ovalbumin* (OA: 0.5 ml of 15% solution) every other day for 3 days. After 4 weeks the guinea pigs were killed b y cervical dislocation. The lungs were immediately removed and placed in cold oxygenated Krebs--Henseleit solution. Six lung strips of a b o u t 25 X 3 X 2 mm were prepared (Lulich et al., 1976) from each guinea-pig lung and simultaneously m o u n t e d in isolated tissue baths containing Krebs--Henseleit solution bubbled with 5% CO2 in O2 at 37°C. Tissues were allowed to stabilize for at least 1 h under a 2 g resting tension. Cumulative concentration--response curves to histamine were recorded with an E & M Isotonic Myograph Transducer con* Egg albumin: ovalbumin, crystallized and lyophilized, Grade III, Sigma Chemical Company, St. Louis, Missouri, U.S.A.
nected to a Fisher Recordall Series 5000 pen recorder via a Narco Physiograph. A predetermined concentration of an antagonist was then added to o n e strip of each pair. Tissues were challenged 60 min later with OA (5 pg ml-1). OA-induced contraction was expressed as the % of the maximum histamine response. Drug doses are expressed in final molar (M) bath concentration. GPLS normally respond to dimaprit (10 -7 to 10 -4) and low concentrations (10 -'° to 10 -7 ) of histamine with relaxation followed b y contraction to higher doses of histamine (>10-7). Relaxation to histamine (10 -'° to 10 -~) was either absent (n = 5/39} or markedly diminished (n = 7/39) in the lung strips of sensitized guinea pigs (n = 39). OA (1--100 pgm1-1) contracted only sensitized GPLS b u t was inactive on unsensitized GPLS (n = 9). OA (5 pg ml-')-induced contractions were equivalent to the maximal histamine response and were sustained f o r 60 to 120 min. Dimaprit (a highly selective histamine H:receptor agonist) (Parsons et al., 1977) reversed pre,existing anaphylactic contractions o f GPLS dose
337
Rapid communication IN VITRO A N A P H Y L A X I S IN GUINEA-PIG LUNG: EVIDENCE F O R THE PROTECTIVE R O L E OF HISTAMINE H2-RECEPTORS N. CHAND Ddpartement d'Anatomie et Physiologie animales, Facultd de Mddecine vdtdrinaire, Universitd de Montrdal, Saint-Hyacinthe, Qudbec, Canada J2S 7C6 Received 14 March 1979, accepted 20 March 1979
The H2-antagonist metiamide has been reported to potentiate in vitro allergic bronchoconstriction in man (Dunlop and Smith, 1977) and the in vivo pulmonary anaphylactic response in the guinea-pig (Drazen et al., 1978). The occurrence of H2-receptors mediating relaxation in the peripheral airway of guinea pig has been established (Chand and DeRoth, 1978}. We n o w demonstrate the protective role of H2-receptors in in vitro anaphylaxis (Schultz-Dale phenomenon) in the guinea-pig lung parenchymal strip (GPLS: peripheral airways: bronchiolar-alveolar ducts and alveoli, Lulich et al., 1976). Guinea-pigs (n = 39) of either sex, weighing 500--800 g were sensitized b y i.p. injection of ovalbumin* (OA: 0.5 ml of 15% solution) every other day for 3 days. After 4 weeks the guinea pigs were killed b y cervical dislocation. The lungs were immediately removed and placed in cold oxygenated Krebs--Henseleit solution. Six lung strips of a b o u t 25 X 3 X 2 mm were prepared (Lulich et al., 1976) from each guinea-pig lung and simultaneously m o u n t e d in isolated tissue baths containing Krebs--Henseleit solution bubbled with 5% CO2 in O2 at 37°C. Tissues were allowed to stabilize for at least 1 h under a 2 g resting tension. Cumulative concentration--response curves to histamine were recorded with an E & M Isotonic Myograph Transducer con* Egg albumin: ovalbumin, crystallized and lyophilized, Grade III, Sigma Chemical Company, St. Louis, Missouri, U.S.A.
nected to a Fisher Recordall Series 5000 pen recorder via a Narco Physiograph. A predetermined concentration of an antagonist was then added to o n e strip of each pair. Tissues were challenged 60 min later with OA (5 pg ml-1). OA-induced contraction was expressed as the % of the maximum histamine response. Drug doses are expressed in final molar (M) bath concentration. GPLS normally respond to dimaprit (10 -7 to 10 -4) and low concentrations (10 -'° to 10 -7 ) of histamine with relaxation followed b y contraction to higher doses of histamine (>10-7). Relaxation to histamine (10 -'° to 10 -~) was either absent (n = 5/39} or markedly diminished (n = 7/39) in the lung strips of sensitized guinea pigs (n = 39). OA (1--100 pgm1-1) contracted only sensitized GPLS b u t was inactive on unsensitized GPLS (n = 9). OA (5 pg ml-')-induced contractions were equivalent to the maximal histamine response and were sustained f o r 60 to 120 min. Dimaprit (a highly selective histamine H:receptor agonist) (Parsons et al., 1977) reversed pre,existing anaphylactic contractions o f GPLS dose
