Paper Information

Journal:   DARU JOURNAL OF PHARMACEUTICAL SCIENCE   2003 , Volume 11 , Number 4; Page(s) 129 To 136.
 
Paper: 

PHARMACOLOGIC CHARACTERIZATION OF BRONCHOSPASM INDUCED BY SUBSTANCE P (SP) AND SP FRAGMENTS IN GUINEA-PIG

 
 
Author(s):  JAFARIAN DOHKORDI A.*, BIGGS D.F.
 
* FACULTY OF PHARMACY AND PHARMACEUTICAL SCIENCES, ISFAHAN UNIVERSITY OF MEDICAL SCIENCES, ISFAHAN, IRAN
 
Abstract: 

Using pharmacologic approach, neurokinin receptor-mediated bronchoconstrictor responses in anesthetized guinea-pigs was characterized. Thus, the bronchospastic effects of substance P (SP) and SP fragments (all administrated intravenously) before and after giving vehicle or selective neurokinin receptor antagonists were compared. Ranking order of potency of SP or SP fragments for induction of bronchoconstriction was: SP>>4-11 >> SP5-11 = SP3-11 = SP2-11 > SP = SP6-11 (the number of amino acid in the sequence of SP fragments is shown by superscript). The neurokinin 1 (NK 1) receptor antagonists (CP 96,345 or CP 99,994, 3 mg kg-1, iv) did not change baseline values of pulmonary flow resistance (RL) and dynamic pulmonary elastance (EL) and did not e liminate bronchopulmonary responses t o these peptides but decreased changes in RL and EL in response to SP and SP fragments. The neurokinin 2 (NK2) receptor antagonist SR 48,968 (1 mg kg-1, iv) failed to induce a rightward shift in dose-response curves to SP or SP fragments except to SP4-11 . Combinations of NK 1 and NK2 receptor antagonists shifted dose-response curves to SP and SP fragments more than that of NKI receptor antagonists alone. These findings reveal that SP-induced bronchoconstriction is mediated by its Cterminal sequence and this response is mainly via NKI receptors. Moreover, bronchopulmonary responses to SP and its C-terminal fragments is complex and there may be interactions between NK1 and NK2 receptors in the lungs.

 
Keyword(s): SUBSTANCE P, SUBSTANCE P FRAGMENTS, NEUROKININ RECEPTOR ANTAGONIST, BRONCHOSPASM, GUINEA-PIG
 
References: 
 
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