The azapirones (buspirone, ipsapirone, gepirone) are partial 5-HT1A receptor agonists that stimulate PRL, GH and cortisol secretion and lower body temperature.40 5-HT1A receptors are sited both presynaptically (cell body autoreceptors) and postsynaptically41-44 so that responses to challenge by these compounds could reflect pre- and/or postsynaptic receptor stimulation. Pindolol has been shown to antagonize the GH response to buspirone, the cortisol response to ipsapirone and the hypothermic responses to buspirone and ipsapirone45-47 suggesting that these are mediated by 5-HT1A receptors. The PRL response to buspirone is particularly robust but the weight of evidence suggests that this is mediated by blockade of dopaminergic (D2) receptors,48 in particular the failure of pindol to antagonize the response in the same study where GH and hypothermic responses were blocked.45 The GH and cortisol responses are likely to reflect postsynaptic activation but there is controversy as to whether the hypothermic response is presynaptic or postsynaptic. In the mouse, presynaptic mediation of 5-HT1A receptor-induced hypothermia is suggested by its attenuation following inhibition of 5-HT synthesis using p-chlorophenylalanine and 5-HT neuronal destruction using 5,7-dihydroxytryptamine49,50 but similar lesions in the rat have produced conflicting results51,52 as have results using raphe micro-injection of 5-HT1A receptor agonists.53,54 In a preliminary report in humans, reducing presynaptic 5-HT function using acute tryptophan depletion failed to affect the hypothermic response to buspirone55 consistent with a postsynaptic mechanism; however a single small negative study such as this is not definitive.
Sumatriptan is a 5-HT1D receptor agonist which increases plasma GH with a variable effect in decreasing plasma PRL.56-59 Cyproheptadine antagonizes the GH response suggesting 5-HT involvement but this agent is a non-selective 5-HT receptor antagonist with uncertain effects at 5-HT1D receptors.56 However the finding that another 5-HT1D receptor agonist, rizatriptan, also elevates GH59 is suggestive of 5-HT1D mediation of the response. 5-HT1D receptors act as terminal autoreceptors on 5-HT neurons and also occur on postsynaptic sites.60 If the reduction in plasma PRL concentration is a real effect of sumatriptan it is likely to reflect a presynaptic action but the site of the receptor mediating the GH response is unknown.
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It seems like you hear it all the time from nearly every one you know I'm SO stressed out!? Pressures abound in this world today. Those pressures cause stress and anxiety, and often we are ill-equipped to deal with those stressors that trigger anxiety and other feelings that can make us sick. Literally, sick.