Differential regulation of smooth muscle contraction in rabbit internal anal sphincter by substance P and bombesin.
Substance P and bombesin induce contraction of isolated IAS smooth muscle cells by different intracellular mechanisms. The cells contracted in a dose dependent manner to both peptides. The kinetics of contraction were different. Substance P induced contraction peaked at 30 seconds and declined in a time dependent manner while bombesin induced contraction peaked at 30 seconds and was maintained for up to 8 minutes. The absence of extracellular calcium in the medium (0 calcium and 2 mM EGTA) had no affect on substance P induced contraction while it blocked bombesin induced contraction. Substance P induced contraction was blocked by the calmodulin antagonist W7 (10(-9)M) and was not affected by the PKC antagonist H7 (10(-6)M). Bombesin induced contraction was blocked by the PKC antagonist H7 and was not affected by the calmodulin antagonist W7. Our data indicate that substance P induces a transient contraction utilizing intracellular calcium and a calmodulin dependent pathway, while bombesin induces a sustained contraction utilizing calcium from extracellular sources and a calmodulin independent pathway.
Division of Pediatric Gastroenterology, University of Michigan Medical Center, Ann Arbor 48109-0658.
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D001003:Anal Canal / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D011493:Protein Kinase C / Q000502:physiology; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D001839:Bombesin; D002118:Calcium