Histamine, endogenous prostaglandins and cyclic nucleotides in the regulation of airway muscle responses in the guinea pig.
Indomethacin (30 mg/kg, i.p.) reduced pulmonary resistance in guinea pigs but did not affect their sensitivity to histamine. This treatment preferentially reduced the generation of PGE2 by isolated tracheal preparations. The ratios of PGF2 alpha/PGE2 before and after treatment were 1/1 and 6/1, respectively. Chronic indomethacin treatment (30 mg/kg, i.p., twice a day for 4 days) increased histamine sensitivity in vivo 2 fold while a longer treatment (10 days) was without effect. The efficacy of histamine and the potency of isoproterenol in tracheal tissues were unaffected by either treatment. Indomethacin (17 microM for 30 min) relaxed tracheal tissues but not bronchial tissues. Responses of both tissues to contractile agonists were potentiated after indomethacin treatment. The efficacy of histamine was smaller in bronchi than in tracheas. Similarly, PGE2, PGI2 and isoproterenol were less potent in bronchi. Basal amounts of cyclic AMP were higher in bronchi than in tracheas; indomethacin did not affect the basal amounts of cyclic AMP in tracheal tissues but reduced them in bronchial preparations. Histamine elevated cyclic AMP content in both preparations; this elevation was reduced by indomethacin. While prostaglandins play a role in modulating airway responses in vitro, their role in airways in normal animals in vivo is more difficult to demonstrate.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001980:Bronchi / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*; D014132:Trachea / Q000502:physiology
D009712:Nucleotides, Cyclic; D011453:Prostaglandins; D006632:Histamine; D000242:Cyclic AMP; D006152:Cyclic GMP; D007213:Indomethacin