Comparison of the bronchoconstrictor and cardiovascular effects of some tachykinins in guinea pigs.
The effects of three tachykinins [substance P (SP), physalaemin (PH), and eledoisin-related peptide (ERP)] were investigated in anesthetized paralyzed guinea pigs. We measured airway resistance (R) and dynamic thoracic elastance (E) with a computerized technique, and blood pressure via a carotid artery. Tachykinins injected iv or intra-aortically (ia) induced dose-dependent increases in R and E, 4 times greater on iv than ia injection. They did not give rise to tachyphylaxis. As a bronchoconstrictor, PH was 5.0X and ERP 1.8X more potent than SP; time to peak response was longer for PH than for ERP and SP; and hypotensive responses, which were of similar magnitude for all three substances, lasted longest after PH. Bronchoconstrictor responses were unaltered by bilateral vagotomy, atropine, mecamylamine, and mepyramine. Morphine reduced PH-induced increases in R (P less than 0.01) and E (P less than 0.05), which were not reversed by naloxone, and capsaicin treatment 1 week before the experiments reduced both SP- and PH-induced increases in E (P less than 0.05). [D-Pro2,D-Trp7,9]-SP reduced ERP-induced increases in R and E, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP reduced both SP- and PH-induced increases in R and E. We conclude that PH is the most potent bronchoconstrictor of the tachykinins tested. Tachykinin-induced bronchospasm is 'non-reflex' arising via a direct effect on airway smooth muscle; the release of histamine, acetylcholine, or other tachykinins is not involved in the responses. [D-Pro2,D-Trp7,9]-SP is more effective at SP-E receptors, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP at SP-P receptors; both types of receptor are located all along the airways.
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D004600:Eledoisin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007705:Kinins / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010803:Physalaemin / Q000494:pharmacology*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D007705:Kinins; C019092:substance P analog(eledoisin related peptide); D010803:Physalaemin; D013373:Substance P; D004600:Eledoisin; D009020:Morphine; D002211:Capsaicin