F Y Lam — Page 2 | PubMed Health

PubMed1989

Inhibition of carrageenan induced inflammation in the rat knee joint by substance P antagonist.

The pathophysiology of acute joint inflammation remains unclear. Evidence is available to suggest a neurally mediated component to the inflammatory process. Acute joint inflammation in the rat knee, induced by intra-articular injection of 2% carrageenan, was reduced by 44% in animals whose knee had previously been injected with 1% capsaicin, while chronic joint denervation produced a 37% reduction. These results indicate a significant neurogenic component in this model of acute joint inflammation. Substance P may be the mediator of this response as intra-articular injection of this agent provoked an acute inflammatory response. Pretreatment of the test knee with the substance P antagonist d-Pro4,d-Trp7 9 10-SP(4-11), however, resulted in a 93% reduction of the inflammatory response to carrageenan. This unexpectedly large effect suggests that this substance P antagonist blocks both neurogenic and non-neurogenic mediators of inflammation. Sympathetic efferent fibres innervating the knee joint were not found to contribute to the neurogenic component of the inflammatory process.

Animals↗

PubMed1985

Cyclic nucleotides and contractility of isolated soleus muscle.

The effects of isoprenaline, terbutaline and forskolin were examined on cyclic nucleotide concentrations and contractile responses in guinea-pig isolated soleus muscles. Isoprenaline and terbutaline induced rapid, concentration-related reductions in the tension and degree of fusion of subtetanic contractions of the soleus muscle. These changes were associated with increases (about 2 fold) in the levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the muscle cells. Propranolol competitively inhibited these responses. Forskolin failed to elicit a sympathomimetic response in the soleus muscles despite increasing (by about 20 fold) the intracellular concentration of cyclic AMP. Forskolin also failed to potentiate the effects induced by isoprenaline. The levels of cyclic GMP in the soleus were increased by isoprenaline (about 1.5 fold) and forskolin (about 2.5 fold). Terbutaline was without effect on cyclic GMP levels. These data suggest either that cyclic AMP is not involved as the mediator underlying beta-adrenoceptor-induced changes in contractility of slow contracting skeletal muscles or that forskolin does not stimulate the particular adenylate cyclase that leads to appropriate increases in cyclic AMP in those functional compartments associated with modulation of intracellular Ca2+ movements. Cyclic GMP is not involved in modifying changes in contractility of the soleus muscle.

Animals↗