Transmitter release, suppression

NPY produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, respiratory depression, and activation of the hypothalamic-pituitary-adrenal axis. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional neuronal actions include inhibition of transmitter release from sympathetic and parasympathetic nerves. Vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. 

It has been demonstrated that cannabinoids act to suppress action potential-evoked calcium rises in the presynaptic terminal, thereby decreasing transmitter release. The action potential-evoked rise in intraterminal calcium was decreased by postsynaptic depolarization. This postsynaptic depolarization induced reduction of presynaptic calcium was prevented by application of antagonists to the CBi receptor (Kreitzer and Regehr, 2001). Cannabinoid-induced decreases in synaptic transmission have been shown to result from an inhibition of N- and P/Q-type calcium channels, the subtypes through which calcium influx occurs during evoked transmitter release (Twitchell et al., 1997). 

The Y2 receptor is the predominant NPY receptor type in the rat brain and such receptors are particularly numerous in the hippocampus (Dumont et al., 1992). Many Y2 receptor-mediated effects have been linked to suppression of transmitter release. For instance, the release of glutamate from terminals synapsing on to rat hippocampal CA1 neurons is inhibited by activation of Y2 receptors. Peripheral Y2 receptors are associated with suppression of transmitter release from sympathetic, parasympathetic and sensory C-fibres. Table 3 summarizes these effects. 

Suppression of transmitter release Antisecretory effect Inhibition of lipolysis Vasoconstriction... 

The acute CNS effects of MDMA administration are mediated by the release of monoamine transmitters, with the subsequent activation of presynaptic and postsynaptic receptor sites.40 As specific examples in rats, MDMA suppresses 5-HT cell firing, evokes neuroendocrine secretion, and stimulates locomotor activity. MDMA-induced suppression of 5-HT cell firing in the dorsal and median raphe involves activation of presynaptic 5-HT1A autoreceptors by endogenous 5-HT.4142 Neuroendocrine effects of MDMA include secretion of prolactin from the anterior pituitary and corticosterone from the adrenal glands 43 Evidence supports the notion that these MDMA-induced hormonal effects are mediated via postsynaptic 5-HT2 receptors in the hypothalamus, which are activated by released 5-HT. MDMA elicits a unique profile of locomotor effects characterized by forward locomotion and elements of the 5-HT behavioral syndrome such as flattened body posture, Straub tail, and forepaw treading.44 6 The complex motor effects of MDMA are dependent on monoamine release followed by activation of multiple postsynaptic 5-HT and DA receptor subtypes in the brain,47 but the precise role of specific receptor subtypes is still under investigation. 

These events happen in a very rapid sequence. However, there is inertia in the system that maintains every impulse as a discrete event. When an impulse reaches the synapse, Ca++ channels open, vesicles with the transmitter substance fuse with the membrane, and the transmitter substance is released into the synaptic cleft. Transmitter substances act as keys for the gates on ion channels at the postsynaptic membrane. The transmitter substance from inhibitory synapses (e.g., GABA) opens CP channels that suppress or stop the action of Na+ influx on the voltage difference, and the positive feedback this has on the Na+ channels. 

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