Prostacyclin activates tachykinin release from capsaicin-sensitive afferents in guinea-pig bronchi through a ruthenium red-sensitive pathway.
1. We have investigated the ability of prostacyclin (PGI2) to contract guinea-pig isolated bronchi and the possible involvement of capsaicin-sensitive primary afferents in the response to PGI2. 2. PGI2 (0.1-100 microM) produced concentration-dependent contractions of the guinea-pig isolated bronchi. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced the PGI2-induced contraction at all concentrations tested. A capsaicin-resistant component of contraction (40-60% of the overall response) was also evident. 3. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, significantly decreased PGI2-induced contractions, without affecting the response to substance P, neurokinin A or acetylcholine. 4. MEN 10, 207, (Tyr5, D-Trp6,8,9, Arg10)-neurokinin A (4-10) (3 microM), a selective antagonist of NK2-tachykinin receptors, significantly decreased PGI2-induced contractions and neurokinin A-induced contractions, without affecting the response to acetylcholine. 5. The effect of ruthenium red and MEN 10,207 on the one hand, and that of ruthenium red and capsaicin on the other was non additive. 6. These results indicate that PGI2-induced contraction of the guinea-pig isolated bronchi involves two distinct mechanisms, one of which involves transmitter (tachykinins) release from peripheral endings of capsaicin-sensitive primary afferents. In as much as PGI2-activation of primary afferents is sensitive to ruthenium red, we suggest that PGI2 shares a common mechanism of tachykinin release with that activated by capsaicin.
Mapp
C E
CE
Institute of Occupational Medicine, University of Padua, Italy.
Fabbri
L M
LM
Boniotti
A
A
Maggi
C A
CA
D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation; D002211:Capsaicin / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D012430:Ruthenium Red / Q000494:pharmacology; D015320:Tachykinins / Q000378:metabolism*
D007202:Indicators and Reagents; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D015320:Tachykinins; D012430:Ruthenium Red; C063615:neurokinin A (4-10), Tyr(5)-Trp(6,8,9)-Arg(10)-; D015288:Neurokinin A; D011464:Epoprostenol; D002211:Capsaicin