Effects of calcitonin gene-related peptide on intracellular calcium concentration in longitudinal muscle of guinea pig ileum

Abstract

The effect of rat calcitonin gene-related peptide (rCGRP) on intracellular free calcium concentration ([Ca 2+] i) and its relationship with muscle relaxation were examined in plexus-free longitudinal muscle (LM) of the guinea pig ileum using a [Ca 2+] i-tension simultaneous recording technique. Tissue was stimulated with either histamine (0.5 μM) or KCl (30 m M). rCGRP at a concentration of 263 n M (which displayed maximal relaxation of the LM) caused a small and brief but significant decrease in the [Ca 2+] i in histamine-treated tissue. On the other hand, the same concentration of rCGRP relaxed the muscle without affecting the [Ca 2+] i in KCl-treated tissue. rCGRP caused a dissociation between the changes in [Ca 2+] i and tension. The effects of forskolin (0.5 μ M) and nifedipine (10 n M) on both [Ca 2−] i and tension were examined in comparison with rCGRP. Forskolin lowered the tension to greater extent than the [Ca 2+] i whereas nifedipine (10 n M) diminished both the [Ca 2+] i and tension in a parallel manner in histamine-treated tissues. These results suggest that rCGRP may not reduce [Ca 2+] i as its primary mechanism of relaxation and it may change the calcium sensitivity of the contractile elements of the smooth muscle.