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 mu M) 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 mu M) 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 Ca2+ channel blocker nifedipine (2 mu M) 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. (c) 2007 Elsevier B.V. All rights reserved.