Prejunctional and postjunctional actions of heptanol and 18 beta-glycyrretinic acid in the rodent vas deferens.
Heptanol and 18 beta-glycyrrhetinic acid (18 beta GA) block gap junctions, but have other actions on transmitter release that have not been characterised. This study investigates the prejunctional and postjunctional effects of these compounds in guinea pig and mouse vas deferens using intracellular electrophysiological recording and confocal Ca(2+) imaging of sympathetic nerve terminals. In mice, heptanol (2 mM) reversibly decreased the amplitude of purinergic excitatory junction potentials (EJPs; 52+/-5%, P<0.05) while having little effect on spontaneous excitatory junction potentials (sEJPs). Heptanol (2 mM) reversibly abolished the nerve terminal Ca(2+) transient in 52% of terminals. 18 beta GA (10 microM) decreased the mean EJP amplitude, and increased input resistance in both mouse (137+/-17%, P<0.05) and guinea pig (354+/-50%, P<0.001) vas deferens indicating gap junction blockade. Further, 18 beta GA increased the sEJP frequency significantly in guinea pigs (by 71+/-25%, P<0.05) and in 5 out of 6 tissues in mice (19+/-3%, P<0.05). Moreover, 18 beta GA depolarised cells from both mice (11+/-1%, P<0.01) and guinea pigs (8+/-1%, P<0.005). Therefore, we conclude that heptanol (2 mM) decreases neurotransmitter release (given the decrease in EJP amplitude) by abolishing the nerve terminal action potential in a proportion of nerve terminals. 18 betaGA (10 microM) effectively blocks the gap junctions, but the increase in sEJP frequency suggests an additional prejunctional effect, which might involve the induction of spontaneous nerve terminal action potentials.
Department of Pharmacology, University of Oxford, Mansfield Rd., Oxford, OX3 0RP, UK.
Faisal
F
Rahman
Rohit
R
Manchanda
Keith L
KL
Brain
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D017097:Electric Impedance; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006168:Guinea Pigs; D019850:Heptanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D014649:Vas Deferens / Q000166:cytology*
D000893:Anti-Inflammatory Agents; D019850:Heptanol; D006034:Glycyrrhetinic Acid; D002118:Calcium