Blockade of nitric oxide-evoked smooth muscle contractions by an inhibitor of guanylyl cyclase.
Nitric oxide-induced contractile responses of smooth muscle were studied in vitro in guinea-pig small intestine. Application of nitric oxide (NO; 0.3-30 microM) evoked a small initial relaxation followed by a marked contractile response in plexus-containing longitudinal smooth muscle preparations from small intestine. The extent of the NO-evoked contractile response was dose-dependent and the response was blocked by tetrodotoxin. Atropine significantly reduced the NO-evoked contraction and the remaining part was abolished by the NK1-receptor antagonist CP 96,345. An inhibitor of soluble guanylyl cyclase, ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one), abolished the NO-evoked contractile response. The results suggest that NO, in addition to the classical direct smooth muscle relaxing effect, causes activation of excitatory neurones, via a pathway utilizing soluble guanylyl cyclase, which leads to a smooth muscle contraction.
Olgart
C
C
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Wiklund
N P
NP
Gustafsson
L E
LE
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D064729:Neurokinin-1 Receptor Antagonists; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013373:Substance P / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology
D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D009569:Nitric Oxide; D013373:Substance P; D013779:Tetrodotoxin; D006162:Guanylate Cyclase; C066892:CP 96345