EFFECTS OF CALCITONIN-GENE-RELATED PEPTIDE ON INTRACELLULAR CALCIUM-CONCENTRATION IN LONGITUDINAL MUSCLE OF GUINEA-PIG ILEUM

The effect of rat calcitonin gene-related peptide (rCGRP) on intracell ular free calcium concentration ([Ca2+](i)) and its relationship with muscle relaxation were examined in plexus-free longitudinal muscle (LM ) of the guinea pig ileum using a [Ca2+](i)-tension simultaneous recor ding technique. Tissue was stimulated with either histamine (0.5 mu M) or KCl (30 mM), rCGRP at a concentration of 263 nM (which displayed m aximal relaxation of the LM) caused a small and brief but significant decrease in the [Ca2+](i) in histamine-treated tissue. On the other ha nd, the same 2+ concentration of rCGRP relaxed the muscle without affe cting the [Ca2+](i) in KCl-treated tissue. rCGRP caused a dissociation between the changes in [Ca2+](i) and tension. The effects of forskoli n (0.5 mu M) and nifedipine (10 nM) on both [Ca2+](i) and tension were examined in comparison with rCGRP. Forskolin lowered the tension to g reater extent than the [Ca2+](i) whereas nifedipine (10 nM) diminished both the [Ca2+](i) and tension in a parallel manner in histamine-trea ted tissues. These results suggest that rCGRP may not reduce [Ca2+](i) as its primary mechanism of relaxation and it may change the calcium sensitivity of the contractile elements of the smooth muscle.