SUPPRESSION BY MUSCARINIC M2 STIMULATION OF THE CONTRACTILE MECHANISM VIA HISTAMINE H-1 RECEPTORS IN THE LONGITUDINAL MUSCLE OF GUINEA-PIG ILEUM

  • 1 May 1987
    • journal article
    • research article
    • Vol. 241  (2) , 587-593
Abstract
The longitudinal muscle of the guinea pig ileum is well known to contract in response to stimulation of either muscarinic or histamine H1 receptors. However, we found that simultaneous application of agonists to both receptors, methacholine (MeCh) and histamine (Hist), at their maximum concentrations (both at 10-5 M), induced a contraction of the muscle with a pattern very similar to that observed with MeCh alone. In the muscle contracted by MeCh, a muscarinic antagonist, atropine, caused a transient relaxation, but a histamine H1 blocker, pyrilamine, had no effect on the tension. Experiments using pirenzepine indicated that muscarinic-M1 receptors did not seem to be involved in the mechanism of this phenomenon. The atropine-induced relaxation was not affected by phentolamine (10-6 M), propranolol (10-6 M) or tetrodotoxin (10-6 M). After pretreatment of the muscle with 10-5 M MeCh for 10 min, the contractile effect of 10-5 M Hist was suppressed intensely for a certain time period, but that of 10-5 M MeCh was not diminished. On the other hand, pretreatment of the muscle with 10-5 M Hist for 10 min did not influence the contraction by either MeCh or Hist. The suppression by MeCh of the Hist action developed dependently on the concentration of MeCh and the time length of exposure to MeCh, and the persistence was temperature-dependent. Furthermore, this suppression was not surmounted by the elevation of Hist concentration. A similar phenonemon was also observed in the muscle which was immersed in the nutrient solution without CaCl2. These results indicate that the stimulation of muscarinic M2 receptors strongly suppresses the contractile effect via histamine H1 receptors, and suggest that this suppression is due to accumulation in the smooth muscle cells of some undefined inhibitory factor(s) which is produced, presumably, through a Ca++-independent pathway triggered by stimulation of muscarinic M2 receptors.