Action of &amp;Delta;&lt;sup&gt;9&lt;/sup&gt;-Tetrahydrocannabinol on Cell Division and Macromolecular Synthesis in Division-Synchronized Protozoa

McClean, Daniel; Zimmerman, Arthur M.

doi:10.1159/000136610

Cited by 53 publications

(41 citation statements)

References 11 publications

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“…This hypothesis also is supported by observations that THC affects brain function and social behavior in ants (49) as well as cyclic nucleotide metabolism and macromolecular synthesis in synchronously dividing protozoa (50,51). Results of the present study suggest that anandamide also may have an ancient origin in evolutionary history.…”

Section: Resultssupporting

confidence: 87%

Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction.

Schuel

Goldstein

Mechoulam

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

165

111

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Anandamide (arachidonylethanolamide) is an endogenous cannabinoid receptor agonist in mammalian brain. Sea urchin sperm contain a high-affinity cannabinoid receptor similar to the cannabinoid receptor in mammalia brain. (-)-A9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in marihuana, reduces the fertilizing capacity of sea urchin sperm by blocking the acrosome reaction that normally is stimulated by a specific ligand in the egg'sjelly coat. We now report that ananda e produces effects similar to those previously obtained with THC in Strongylocentrotus purpuratus in reducing sperm fertilizing capacity and inhibiting the egg jelly-stimulated acrosome reaction. Arachidonic acid does not inhibit the acrosome reaction under similar conditions. The adverse effects of anandamide on sperm fertilizing capacity and the acrosome reaction are reversible. The receptivity of unfertilized eggs to sperm and sperm motility are not impaired by anandamide. Under conditions where anandamide completely blocks the eggjelly-stimulated acrosome reaction, it does not inhibit the acrosome reaction artificially initiated by ionomycin, which promotes Ca+ influx, and nigericin, which activates K+ channels in sperm. These findings provide additional evidence that the annabnoid receptor in sperm plays a role in bloing the acrosome reaction, indicate that anandamide or a related molecule may be the natural ligand for the cannabinoid receptor in sea urchin sperm, and suggest that binding of anandamide to the cannabinoid receptor modulates stimulus-secretion-coupling in sperm by affecting an event prior to ion channel opening.

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Section: Resultssupporting

confidence: 87%

Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction.

Schuel

Goldstein

Mechoulam

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

165

111

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“…For example, McClean & Zimmerman (1976) reported the e¡ects of Á 9 THC on cell division and macromolecular synthesis in the protozoan Tetrahymena pyriformis, whilst Waser (1979) reported the e¡ects of Á 9 THC on behaviour in ants. Turkanis & Karler (1988) reported an example of a study in which the in vitro pharmacological e¡ects of cannabinoids on an invertebrate species were examined.…”

Section: (B) Comparative Pharmacology Of Cannabinoidsmentioning

confidence: 99%

The neurobiology and evolution of cannabinoid signalling

Elphick

Egertová

2001

Phil. Trans. R. Soc. Lond. B

354

261

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The plant Cannabis sativa has been used by humans for thousands of years because of its psychoactivity. The major psychoactive ingredient of cannabis is δ 9 –tetrahydrocannabinol, which exerts effects in the brain by binding to a G–protein–coupled receptor known as the CB 1 cannabinoid receptor. The discovery of this receptor indicated that endogenous cannabinoids may occur in the brain, which act as physiological ligands for CB 1 . Two putative endocannabinoid ligands, arachidonylethanolamide (‘anandamide’) and 2–arachidonylglycerol, have been identified, giving rise to the concept of a cannabinoid signalling system. Little is known about how or where these compounds are synthesized in the brain and how this relates to CB 1 expression. However, detailed neuroanatomical and electrophysiological analysis of mammalian nervous systems has revealed that the CB 1 receptor is targeted to the presynaptic terminals of neurons where it acts to inhibit release of ‘classical’ neurotransmitters. Moreover, an enzyme that inactivates endocannabinoids, fatty acid amide hydrolase, appears to be preferentially targeted to the somatodendritic compartment of neurons that are postsynaptic to CB 1 –expressing axon terminals. Based on these findings, we present here a model of cannabinoid signalling in which anandamide is synthesized by postsynaptic cells and acts as a retrograde messenger molecule to modulate neurotransmitter release from presynaptic terminals. Using this model as a framework, we discuss the role of cannabinoid signalling in different regions of the nervous system in relation to the characteristic physiological actions of cannabinoids in mammals, which include effects on movement, memory, pain and smooth muscle contractility. The discovery of the cannabinoid signalling system in mammals has prompted investigation of the occurrence of this pathway in non–mammalian animals. Here we review the evidence for the existence of cannabinoid receptors in non–mammalian vertebrates and invertebrates and discuss the evolution of the cannabinoid signalling system. Genes encoding orthologues of the mammalian CB 1 receptor have been identified in a fish, an amphibian and a bird, indicating that CB 1 receptors may occur throughout the vertebrates. Pharmacological actions of cannabinoids and specific binding sites for cannabinoids have been reported in several invertebrate species, but the molecular basis for these effects is not known. Importantly, however, the genomes of the protostomian invertebrates Drosophila melanogaster and Caenorhabditis elegans do not contain CB 1 orthologues, indicating that CB 1 –like cannabinoid receptors may have evolved after the divergence of deuterostomes (e.g. vertebrates and echinoderms) and protostomes. Phylogenetic analysis of the relationship of vertebrate CB 1 receptors with other G–protein–coupled receptors reveals that the paralogues that appear to share the most recent common evolutionary origin with CB 1 are lysophospholipid receptors, melanocortin receptors and adenosine receptors. Interestingly, as with CB 1 , each of these receptor types does not appear to have Drosophila orthologues , indicating that this group of receptors may not occur in protostomian invertebrates. We conclude that the cannabinoid signalling system may be quite restricted in its phylogenetic distribution, probably occurring only in the deuterostomian clade of the animal kingdom and possibly only in vertebrates.

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“…Similar results were obtained with mice infected with N. fowleri intravenously. DISCUSSION A9-THC inhibits growth of several protozoa (5,14) and mammalian cells (12,18), but does not inhibit growth of selected yeast or bacteria.…”

mentioning

confidence: 97%

“…A9-Tetrahydrocannabinol (A9-THC) has been reported to inhibit the growth of several protozoa, including Dictyostelium discoideum (5) and Tetrahymena pyrifonnis (14). In addition, A9-THC has been reported to retard the proliferation of tumor cells in vivo (16) and in vitro (18).…”

mentioning

confidence: 99%

Susceptibility of Naegleria fowleri to delta 9-tetrahydrocannabinol

Pringle¹,

Bradley²,

Harris³

1979

Antimicrob Agents Chemother

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Growth of the pathogenic amoeboflagellate Naegleria fowleri is inhibited by delta 9-tetrahydrocannabinol (delta 9-THC). delta 9-THC is amoebostatic at 5 to 50 micrograms/ml. delta 9-THC prevents enflagellation and encystment, but does not impair amoeboid movement. Calf serum at 10 and 20% (vol/vol) reduces the antiamoeba activity of delta 9-THC. Only 1-methoxy delta 8-tetrahydrocannabinol, of 17 cannabinoids tested, failed to inhibit growth of N. fowleri. Antinaeglerial activity was not markedly altered by opening the pyran ring, by converting the cyclohexyl ring to an aromatic ring, or by reversing the hydroxyl and pentyl groups on the benzene ring. delta 9-THC prevented the cytopathic effect of N. fowleri on African green monkey (Vero) cells and human epithelioma (HEp-2) cells in culture. delta 9-THC afforded modest protection to mice infected with N. fowleri.

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Action of Δ<sup>9</sup>-Tetrahydrocannabinol on Cell Division and Macromolecular Synthesis in Division-Synchronized Protozoa

Cited by 53 publications

References 11 publications

Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction.

Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction.

The neurobiology and evolution of cannabinoid signalling

Susceptibility of Naegleria fowleri to delta 9-tetrahydrocannabinol

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