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PubMed1998

Protein kinase G expression in the small intestine and functional importance for smooth muscle relaxation.

In functional experiments, the nitric oxide (NO) donor N-morpholino-N-nitroso-aminoacetonitrile or the cGMP analog 8-(4-chlorophenylthio)-cGMP caused a concentration-dependent, tetrodotoxin-resistant relaxation of precontracted strips from rat small intestine. The inhibitory effect of both substances was completely blocked at lower concentrations and was significantly attenuated at higher concentrations by the selective cGMP-dependent protein kinase (cGK) antagonist KT-5823 (1 microM). cGK-I was identified by immunohistochemistry in circular and longitudinal muscle, lamina muscularis mucosae, and smooth muscle cells of the villi and in fibroblast-like cells of the small intestine. Additionally, there was staining of a subpopulation of myenteric and submucous plexus neurons. Double staining for neuronal NO synthase (nNOS) and cGK-I demonstrated a colocalization of these two enzymes. Western blot analysis of smooth muscle preparations and isolated nerve terminals demonstrated that these structures predominantly contain the cGK-Ibeta isoenzyme, whereas the cGK-Ialpha expression is about threefold less. The isoform cGK-II was entirely confined to mucosal epithelial cells. These results show that cGK-I is expressed in different muscular structures of the small intestine and participates in the NO-induced relaxation of gastrointestinal smooth muscle. The presence of cGK-I in NOS-positive enteric neurons further suggests a possible neuronal action site.

Alkaloids↗
PubMed1993

Smooth muscle relaxant effects of propofol and ketamine in isolated guinea-pig trachea.

The effects of anesthetics on airway smooth muscle tone are important in the management of patients with asthma. In the present study we evaluated the effect of propofol and ketamine on isolated guinea-pig tracheal preparations mounted for recording isometric contractile force. In a concentration-dependent way both drugs produced 100% relaxation irrespective of whether tracheal tone was spontaneous or induced by carbachol, histamine, prostaglandin F2 alpha, 30 mM K+ or 124 mM K+. The relaxant potency of propofol was dependent of the formulation of the drug used. Propofol showed an about 3 times higher potency when solubilized with hydroxypropyl-beta-cyclodextrin compared with an oil-in-water emulsion of the drug (Diprivan). Propofol had the greatest potency on tracheal preparations with spontaneous tone (EC50 = 4.0 +/- 0.9 microM). Ketamine preferentially relaxed contractions elicited by carbachol (EC50 = 120.8 +/- 5.2 microM) and had a lower potency than propofol when tone was spontaneous or induced by other tracheal spasmogens. Since propofol was a more effective tracheal relaxant in vitro than ketamine, the possibility that propofol, like ketamine, may inhibit bronchoconstriction during anesthesia should be studied further.

Animals↗