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An endogenous 5-HT(7) receptor mediates pigment granule dispersion in Xenopus laevis melanophores.

ABSTRACT: Melatonin (5-methoxy N-acetyltryptamine) and serotonin (5-HT) exert rapid, but opposite effects on pigment granule distribution in Xenopus laevis melanophores. Low concentrations of melatonin (10(-11) - 10(-9) M) cause a dramatic perinuclear aggregation of the melanin-containing granules, while 5-HT (10(-8) - 10(-5) M) disperses pigment granules throughout the cell. The present study found that pharmacological doses of melatonin (> or =10(-6) M) induced a time- and concentration-dependent pigment granule dispersion, which was mediated by an endogenous melanophore 5-HT receptor. 5-HT produced a concentration-dependent elevation of melanophore cyclic AMP, and 5-HT-induced dispersion was blocked by H89 (10(-4) M), an inhibitor of protein kinase A (PKA), but not by a PKC inhibitor (Ro 31-8220, 10(-5) M), indicating a vital role for cyclic AMP in 5-HT-induced dispersion. 5-HT-mediated dispersion was not blocked by antagonists selective for G(s)-coupled 5-HT(4) (GR113808) or 5-HT(6) (Ro 04-6790, Ro 63-0563, olanzepine) receptors, nor by 5-HT(1 - 3) (pindolol, ketanserine, metoclopramide, MDL72222, tropisetron) receptor antagonists, but was inhibited by a selective 5-HT(7) receptor antagonist, DR4004, and other antagonists with a high affinity for 5-HT(7) receptors. The rank order of antagonist potency was: risperidone (mean pK(B) 7.82)>methiothepin (7.43)>DR4004 (6.92)>mesulergine (6.83)>methysergide (6.60)>[+/-]-sulpiride (5.81)>spiperone (5.52). The agonist potency order [mean pEC(50), 5-CT (8.68)>5-HT (7.13)>5-MT (6.94)>8-OH-DPAT (4.79)>sumatriptan (<4)] was also consistent with an action on 5-HT(7) receptors. RT - PCR confirmed that melanophores express 5-HT(7) receptor mRNA. The pigment dispersing effect of high melatonin concentrations in melanophores is most likely mediated by activation of 5-HT(7) receptors. Conceivably some of the effects attributed to pharmacological doses of melatonin in mammals may be mediated by activation of 5-HT(7) receptors.

SUBMITTER: Teh MT

PROVIDER: S-EPMC1572726 | biostudies-literature | 2001 Apr

REPOSITORIES: biostudies-literature

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An endogenous 5-HT(7) receptor mediates pigment granule dispersion in Xenopus laevis melanophores.

Teh M T MT Sugden D D

British journal of pharmacology 20010401 8

Melatonin (5-methoxy N-acetyltryptamine) and serotonin (5-HT) exert rapid, but opposite effects on pigment granule distribution in Xenopus laevis melanophores. Low concentrations of melatonin (10(-11) - 10(-9) M) cause a dramatic perinuclear aggregation of the melanin-containing granules, while 5-HT (10(-8) - 10(-5) M) disperses pigment granules throughout the cell. The present study found that pharmacological doses of melatonin (> or =10(-6) M) induced a time- and concentration-dependent pigmen ...[more]

PMID: 11309252

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Project description:The global amphibian declines are compounded by infections with members of the Ranavirus genus such as Frog Virus 3 (FV3). Premetamorphic anuran amphibians are believed to be significantly more susceptible to FV3 while this pathogen targets the kidneys of both pre- and postmetamorphic animals. Paradoxically, FV3-challenged Xenopus laevis tadpoles exhibit lower kidney viral loads than adult frogs. Presently, we demonstrate that X. laevis tadpoles are intrinsically more resistant to FV3 kidney infections than cohort-matched metamorphic and postmetamorphic froglets and that this resistance appears to be epigenetically conferred by endogenous retroviruses (ERVs). Using a X. laevis kidney-derived cell line, we show that enhancing ERV gene expression activates cellular double-stranded RNA-sensing pathways, resulting in elevated mRNA levels of antiviral interferon (IFN) cytokines and thus greater anti-FV3 protection. Finally, our results indicate that large esterase-positive myeloid-lineage cells, rather than renal cells, are responsible for the elevated ERV/IFN axis seen in the tadpole kidneys. This conclusion is supported by our observation that CRISPR-Cas9 ablation of colony-stimulating factor-3 results in abolished homing of these myeloid cells to tadpole kidneys, concurrent with significantly abolished tadpole kidney expression of both ERVs and IFNs. We believe that the manuscript marks an important step forward in understanding the mechanisms controlling amphibian antiviral defenses and thus susceptibility and resistance to pathogens like FV3. IMPORTANCE Global amphibian biodiversity is being challenged by pathogens like the Frog Virus 3 (FV3) ranavirus, underlining the need to gain a greater understanding of amphibian antiviral defenses. While it was previously believed that anuran (frog/toad) amphibian tadpoles are more susceptible to FV3, we demonstrated that tadpoles are in fact more resistant to this virus than metamorphic and postmetamorphic froglets. We showed that this resistance is conferred by large myeloid cells within the tadpole kidneys (central FV3 target), which possess an elevated expression of endogenous retroviruses (ERVs). In turn, these ERVs activate cellular double-stranded RNA-sensing pathways, resulting in a greater expression of antiviral interferon cytokines, thereby offering the observed anti-FV3 protection.

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An endogenous 5-HT(7) receptor mediates pigment granule dispersion in Xenopus laevis melanophores.

Publications

An endogenous 5-HT(7) receptor mediates pigment granule dispersion in Xenopus laevis melanophores.

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