Effect of an homologous series of aliphatic alcohols on neuronal and smooth muscle voltage-dependent Ca2+ channels.
The acute inhibitory actions of alcohol on K(+)-stimulated 45Ca2+ uptake into synaptosomes shows regional variation in sensitivity throughout the brain, suggesting the possibility of a selective action on a specific Ca2+ channel subtype. This was examined by comparing the effects of a homologous series of aliphatic alcohols on synaptosomal Ca2+ channels with their actions on K(+)-stimulated Ca2+ channels in guinea-pig intestinal longitudinal muscle, which have been demonstrated to be of the L-type. K(+)-stimulated contraction of and [3H]nitrendipine binding to smooth muscle were both inhibited by the alcohols at similar concentrations, with the potency increasing with chain length. In synaptosomes, however, K(+)-stimulated 45Ca2+ uptake was 5-30 times more sensitive to the inhibitory actions of alcohol than were [3H]nitrendipine and [125I]omega-conotoxin binding. These observations suggest that K(+)-stimulated 45Ca2+ uptake is mediated by a non-L non-N type channel which is more sensitive to the acute effects of alcohols. This is supported by the observation that K(+)-stimulated 45Ca2+ uptake which is insensitive to L- and N-channel antagonists was inhibited by funnel web spider venom.
Hawthorn
M H
MH
Department of Biochemical Pharmacology, School of Pharmacy, SUNY, Buffalo 14260.
Ferrante
J N
JN
Kwon
Y W
YW
Rutledge
A
A
Luchowski
E
E
Bangalore
R
R
Triggle
D J
DJ
D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009568:Nitrendipine / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D020960:omega-Conotoxins
D000438:Alcohols; D002121:Calcium Channel Blockers; D015220:Calcium Channels; C071920:FTX, spider toxin; D010456:Peptides, Cyclic; D011073:Polyamines; D020960:omega-Conotoxins; C053423:Conus magus toxin; D009568:Nitrendipine; D011188:Potassium