n-pentanoyl-2-benzyltryptamine and 6-chloromelatonin

The effects of melatonin on reproductive function were examined using hamster spermatozoa. When 1 pM to 1 microM melatonin was added to the mTALP medium, hyperactivation was significantly enhanced. Antagonists and agonists of the melatonin receptor (i.e., MT1 and MT2) were added to the medium. Luzindole, an MT1 and MT2 competitive antagonist, significantly inhibited melatonin-induced hyperactivation, whereas the MT2-specific antagonists, 4-phenyl-2-propionamidotetralin and N-pentanoyl-2-benzyltryptamine, had no effect. Moreover, hyperactivation was significantly enhanced when non-specific agonists, such as 6-chloromelatonin and 2-iodomelatonin, were added to the medium. 8-Methoxy-2-propionamidotetralin, which is a strong MT2 agonist and a weak MT1 agonist, significantly increased hyperactivation, although the effect was weak. Therefore, it is likely that melatonin enhances sperm hyperactivation via the MT1 receptor.

Topics: Animals; Calcium; Cells, Cultured; Cricetinae; Culture Media; Dose-Response Relationship, Drug; Male; Melatonin; Mesocricetus; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Serum Albumin; Sperm Motility; Spermatozoa; Stimulation, Chemical; Tetrahydronaphthalenes; Time; Tryptamines

Melatonin, its agonists/antagonists were administered intrathecally (i.t.) before/after intradermal injection of capsaicin. Capsaicin produced an increase in the paw withdrawal frequency (PWF) in the presumed area of secondary mechanical allodynia and hyperalgesia. Melatonin agonists in the absence of a capsaicin injection decreased the PWF significantly, whereas melatonin antagonists given intrathecally alone were ineffective in the absence of a capsaicin injection. Pre-treatment with a melatonin agonist i.t. caused a reduction in the PWF after capsaicin. In contrast, the PWF increased after capsaicin with pre-administration of a melatonin antagonist i.t. Combined pre-treatment with melatonin and a melatonin antagonist i.t. prevented the change in PWF induced by melatonin alone after capsaicin. Intrathecal post-treatment with a melatonin agonist reduced the enhanced PWF that followed an injection of capsaicin, but treatment with a combination of a melatonin agonist and its antagonist did not alter the responses. The PWF was unaffected when melatonin analogs were applied i.t. at the T6 level or were injected intramuscularly adjacent to the L4 vertebra. In spinal rats, the data showed comparable effects of melatonin analogs on capsaicin-induced secondary mechanical hyperalgesia. Animal motor function tested by 'activity box' showed that motion activity was not affected by i.t. melatonin or its antagonist. These results suggest that activation of the endogenous melatonin system in the spinal cord can reduce the generation, development and maintenance of central sensitization, with a resultant inhibition of capsaicin-induced secondary mechanical allodynia and hyperalgesia.

Topics: Administration, Topical; Afferent Pathways; Animals; Capsaicin; Disease Models, Animal; Drug Interactions; Hyperalgesia; Injections, Intramuscular; Injections, Spinal; Male; Melatonin; Neural Inhibition; Pain; Physical Stimulation; Rats; Rats, Sprague-Dawley; Reflex; Skin; Spinal Cord; Spinal Cord Injuries; Tetrahydronaphthalenes; Tryptamines