Effect of nedocromil sodium on non-adrenergic, non-cholinergic neural responses in guinea pig bronchi in vitro.
OBJECTIVE
Nedocromil sodium (nedocromil) improves the clinical condition of asthmatic subjects but its mechanism of action is not fully understood. This study aimed to determine whether nedocromil alters the ability of contractile and relaxant non-adrenergic, non-cholinergic neural (NANC) responses to stabilise tone by inhibiting or potentiating these responses in bronchial smooth muscle and, if so, whether the action is on a pre- or postjunctional level.


RESULTS
Nedocromil attenuated contractile but not relaxant NANC responses (elicited by electric field stimulation) significantly (P < 0.05) in guinea pig main bronchi in vitro. However, the ability of NANC responses to stabilise tone (convergence effect) was not significantly impaired by nedocromil. Furthermore, nedocromil did not significantly shift the concentration response curve (-log EC50) to neurokinin A (NKA), the dominating contractile NANC transmitter, or alter the maximum response to NKA (P > 0.05). Submaximum or maximum contractile responses to histamine were not markedly affected by nedocromil (P > 0.05).


CONCLUSIONS
Nedocromil exerts selective neural inhibition of the contractile but not of the relaxant NANC responses on a pre-junctional level in bronchial smooth muscle. Nedocromil does not, however, markedly impair the ability of NANC response to stabilise bronchial smooth muscle tone.
Lindén
A
A
Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Göteborg University, Gothenburg, Sweden. anders.linden@pharm.gu.se
Bergendal
A
A
Lötvall
J
J
Skoogh
B E
BE
Löfdahl
C G
CG
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology*; D001985:Bronchial Provocation Tests; D005260:Female; D006168:Guinea Pigs; D006632:Histamine; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D017835:Nedocromil / Q000494:pharmacology*; D015288:Neurokinin A / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011941:Receptors, Adrenergic / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects
D018927:Anti-Asthmatic Agents; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D017835:Nedocromil; D006632:Histamine; D015288:Neurokinin A