Extract of the marine alga Prymnesium patelliferum induces release of acetylcholine from cholinergic nerves in the rat bronchial smooth muscle.
An extract of the marine algal flagellate Prymnesium patelliferum enhanced the spontaneous as well as the K+ evoked (51 mM K+) release of [3H]acetylcholine and endogenous acetylcholine from autonomic cholinergic nerves of rat bronchial smooth muscle. The effects were concentration-dependent and reversible. The enhancement of the K+ evoked release by the algal extract was partly dependent on extracellular Ca2+ and was significantly suppressed by the organic Ca2+ blockers omega-conotoxin GVIA (1 microM), diltiazem (100 microM), nifedipine (100 microM) and flunarizine (100 microM). The enhancement of the spontaneous release seemed Ca2+ independent and not sensitive to the Na+ channel blocker tetrodotoxin. Sphingosine (20 microM), a protein kinase C inhibitor, strongly potentiated the enhancement of spontaneous release of [3H]acetylcholine induced by the algal extract whereas another protein kinase C inhibitor. 1-(5-quinolinesulphonyl)-2-methylpiperazine (H-7) (20 microM), was without effect. A similar potentiation as seen with sphingosine was observed with procaine (100 microM) and flunarizine (100 microM). The results indicate that the enhancement of the K+ evoked release of [3H]acetylcholine by the toxic extract of P. patelliferum was partly caused by activation of voltage-dependent Ca2+ channels. The increase in the spontaneous release of [3H]acetylcholine and endogenous acetylcholine induced by the algal extract alone may be caused by an ionophore-like property of the algal extract. This effect of the algal extract may be enhanced by compounds that facilitate the interaction of the algal toxin with the plasma membrane such as the lipophilic compounds flunarizine, procaine and sphingosine.
Meldahl
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Division for Environmental Toxicology, Norweigan Defence Research Establishment, Kjeller.
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Fonnum
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D000461:Rhodophyta / Q000737:chemistry*
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D011493:Protein Kinase C; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium