Hsp27 is a mediator of sustained smooth muscle contraction in response to bombesin.
We have identified the low MW 27 kD heat shock protein as a major phosphoprotein constituent of smooth muscle and have investigated its potential role in agonist induced smooth muscle contraction. The neuropeptides bombesin and substance P, which are present in neurons of the anorectal region, induce contraction of isolated smooth muscle cells from this region by activating different intracellular pathways. Substance P-induced contraction is 1,4,5-inositol trisphosphate (IP3)/calmodulin dependent, while contraction induced by bombesin is mediated by a protein kinase C (PKC)-dependent pathway. The sustained contraction induced by bombesin or exogenous PKC was blocked by preincubation of cells with monoclonal antibodies to hsp27, while the transient contraction induced by substance P or IP3 was unaffected by the antibodies. Preincubation with isotype matched control antibodies had no inhibitory effect on contraction induced in response to the agents used. These data support a novel role for hsp27 in the non calmodulin mediated sustained contraction induced by bombesin or PKC.
Bitar
K N
KN
Division of Pediatric Gastroenterology, University of Michigan Medical Center, Ann Arbor 48109-0658.
Kaminski
M S
MS
Hailat
N
N
Cease
K B
KB
Strahler
J R
JR
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001003:Anal Canal / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal; D001839:Bombesin / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D015180:Electrophoresis, Gel, Two-Dimensional; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D006360:Heat-Shock Proteins; D007546:Isoquinolines; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D010879:Piperazines; D013449:Sulfonamides; D013373:Substance P; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D001839:Bombesin