Intercellular communication through gap junctions: a potential role in pharmacomechanical coupling and syncytial tissue contraction in vascular smooth muscle isolated from the human corpus cavernosum.
Kinetic and steady-state protocols were used to examine the effects of disruption of intercellular communication with heptanol, on contractile responses elicited by activation of the alpha 1-adrenergic receptor in human corporal vascular smooth muscle. For the steady-state studies, strips of corporal tissue from 19 patients were submaximally precontracted with phenylephrine (PE) and then relaxed by the cumulative addition of heptanol. Heptanol completely and reversibly relaxed all tissues studied in a concentration-dependent manner. The heptanol concentration response data were then computer fit to the general logistic equation to obtain pEC50 (negative logarithm of the concentration that elicits one-half of the maximal effect) and slope factor values, with Emax (maximal relaxation) set to 100%. The mean pEC50 and slope factor values, respectively, were 2.86 +/- 0.04 and 1.86 +/- 0.17. Furthermore, kinetic studies on corporal tissues from a subset of the patient population (11 patients) revealed that preincubation of tissues with 2 mM heptanol caused a significant decrease in both the rate and magnitude of PE-induced contractions in all tissues studied, without affecting the rate constant for onset of contraction (k(obs)). The present results on intact tissue extend our previous observations on cultured corporal cells, and support the supposition that intercellular communication through gap junctions may play an important role in the initiation, maintenance and modulation of alpha 1-adrenergic contractions in human vascular smooth muscle.
Christ
G J
GJ
Department of Urology Albert Einstein College of Medicine, Bronx, NY 10461.
Moreno
A P
AP
Parker
M E
ME
Gondre
C M
CM
Valcic
M
M
Melman
A
A
Spray
D C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000438:Alcohols / Q000494:pharmacology*; D007172:Erectile Dysfunction / Q000503:physiopathology; D019850:Heptanol; D006801:Humans; D066298:In Vitro Techniques; D007365:Intercellular Junctions / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D010413:Penis / Q000098:blood supply; D010656:Phenylephrine / Q000494:pharmacology
D000438:Alcohols; D010656:Phenylephrine; D019850:Heptanol