It is well established that serotonin (5-HT; 5-hydroxytryptamine) plays a role in mammalian regulation of the hypothalamic-pituitary-adrenal (HPA) axis via the 5-HT receptor subtype 1A (5-HT1A). To date, there has not been a comprehensive investigation of the molecular, pharmacological and physiological aspects of the 5-HT1A receptor and its role in the activation of the hypothalamic-pituitary-interrenal (HPI) axis in teleost fish. The 5-HT1A receptor of the Gulf toadfish (Opsanus beta) was cloned and sequenced, showing 67.5% amino acid similarity to the human homologue. The 5-HT1A receptor was distributed throughout the brain, with the whole brain containing significantly higher levels of 5-HT1A mRNA compared to all other tissues and the midbrain/diencephalon region containing significantly higher levels of transcript than any other brain region. Substantial levels of transcript were also found in the pituitary, while very low levels were in the kidney that contains the interrenal cells. Xenopus oocytes injected with toadfish 5-HT1A receptor cRNA displayed significantly higher binding of [3H]5-HT that was abolished by the mammalian 5-HT1A receptor agonist, 8-OH-DPAT, indicating a conserved binding site of the toadfish 5-HT1A receptor and a high specificity for the agonist. Supporting this, binding of [3H]5-HT was not affected by the mammalian 5-HT1B receptor agonist, 5-nonyloxytryptamine, the 5-HT7 receptor antagonist, SB269970, or the 5-HT2 receptor agonist, α-methylserotonin. Confirming these molecular and pharmacological findings, intravenous injection of 8-OH-DPAT stimulated the HPI axis to cause a 2-fold increase in circulating levels of cortisol. The present study of the 5-HT1A receptor in a single teleost species illustrates the high conservation of this 5-HT receptor amongst vertebrates.
- Hypothalamic-pituitary-adrenal axis
- Hypothalamic-pituitary-interrenal axis
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