The antagonism of histamine-induced tracheal and bronchial muscle contraction by diphenhydramine: effect of maturation.
Airway reactivity in spontaneously breathing unanaesthetized female guinea-pigs was significantly reduced as a consequence of maturation. Threshold doses to histamine (% w/v base) were 0.08% +/- .01 and 0.27% +/- .04 in immature (110 g +/- 2; 1 week old) and mature (837 g +/- 29; 4 months old) animals, respectively. The potency of 2-(2-thiazolyl) ethylamine in tracheal tissues from mature animals was significantly less than that in tissues from immature animals (5.06 +/- .03 vs 5.26 +/- .07). There was no change in the potency of this agonist in bronchial tissues (5.0 +/- .09 vs 4.9 +/- .13). Diphenhydramine reduced tissue contractility in tracheal (30% at 0.1 microM; 50% at 3 microM) but not bronchial tissues. The antihistamine in concentrations ranging from 0.1 microM to 3 microM reduced the potency of histamine 2 to 50 fold in both tissues. Schild plots were linear but slopes were significantly less than unity. pA2 values +/- 95% fiducial limits derived from data from tracheal tissues of immature and mature animals using constrained Schild plots (unit slope) were 7.7 (7.6-7.7) and 7.1 (7.0-7.2), respectively (P less than 0.05). pA2 values for diphenhydramine in bronchial tissues using constrained Schild plots were 7.8 (7.7-7.9) and 7.5 (7.3-7.5), respectively (P less than 0.05). The data emphasize the unique nature of tracheal and bronchial tissues. We conclude that, with maturation, the characteristics of the histamine receptor change. We suggest that the remission of asthma which frequently occurs at puberty may be related to alteration in the properties of membrane receptors.
D000375:Aging; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D004155:Diphenhydramine / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010991:Plethysmography; D014132:Trachea / Q000187:drug effects
D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D006632:Histamine; D004155:Diphenhydramine; D002217:Carbachol