Effects of heptanol and carbenoxolone on noradrenaline induced contractions in guinea pig vas deferens.
We examined the effects of two putative gap junction blockers, heptanol and carbenoxolone, on noradrenaline-induced contractions in guinea pig vas deferens. The force generated due to the exogenously added noradrenaline (20 microM) consisted of two components: the tonic and the oscillatory. 2 mM heptanol abolished the oscillatory contractions and drastically suppressed both the maximum force (by 85.4 +/- 18.2%) as well as the tonic component (by 28.8 +/- 5.1%) (P<0.01, n=7). However, the effects of carbenoxolone (50 microM) were strikingly different, with the spikes of the oscillatory component being merged into a steady, "fused" contraction, without affecting the maximum force developed. The L-type Ca(2+) channel blocker nifedipine (2 microM) abolished the oscillatory component of the contractions and significantly reduced the maximum force and tonic component (by 82.4 +/- 6.8% and 19.7 +/- 6.4% respectively; P<0.01, n=4), in a manner similar to that elicited by heptanol. Our results indicate that (i) while carbenoxolone specifically blocks gap junctions, heptanol appears to exert its actions through non-gap junctional mechanisms, possibly by blocking VGCCs in smooth muscle; (ii) gap junctions play a significant modulatory role in the generation of noradrenaline-induced contractions in guinea pig vas deferens, particularly in the emergence of oscillatory contractions, while the maximum force developed may be independent of gap junctional contribution.
Palani
D
D
Biomedical Engineering Group, School of Biosciences and Bioengineering, Indian Institute of Technology-Bombay, Mumbai-400076, India.
Ghildyal
P
P
Manchanda
Rohit
R
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D019850:Heptanol / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014662:Vasoconstrictor Agents; D019850:Heptanol; D009543:Nifedipine; D002229:Carbenoxolone; D009638:Norepinephrine