Serotonin-induced pulmonary responses in the perfused guinea pig lung: evidence for 5HT2 receptor-mediated pulmonary vascular and airway smooth muscle constriction.
The isolated perfused guinea pig lung was used to investigate pharmacologic characteristics of serotonin receptors in pulmonary vascular and airway smooth muscle. Serotonin caused a marked dose-related increase in pulmonary arterial pressure and peak intratracheal pressure when injected into the pulmonary artery. In contrast to serotonin, 5-carboxamidotryptamine, a 5HT1A and 5HT1B receptor agonist, and 2-methylserotonin, a 5HT3 receptor agonist produced only weak vascular and airway responses. Furthermore, vasoconstriction and bronchoconstriction elicited by serotonin were antagonized by the potent 5HT2 receptor antagonists, LY53857, ketanserin, and ritanserin. Antagonist specificity for 5HT2 receptors was demonstrated in the perfused guinea pig lung since similar responses induced by histamine were not blocked. High concentrations of serotonin were tachyphylactic on vascular but not airway constriction. Tachyphylaxis of vascular responses was not observed to an equipotent concentration of leukotriene D4 (LTD4). Thus, both the pulmonary vascular and airway constriction to serotonin were predominantly due to 5HT2 receptor activation. Furthermore, tachyphylaxis of vascular responses to serotonin might prove useful to differentiate 5HT receptor systems in pulmonary blood vessels from those in airways.
Selig
W M
WM
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285.
Bloomquist
M A
MA
Cohen
M L
ML
Fleisch
J H
JH
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012701:Serotonin