Site of ATP and phenylephrine synergistic stimulation of vasopressin release from the hypothalamo-neurohypophyseal system
Abstract
ATP and norepinephrine are neurotransmitters carrying cardiovascular information to vasopressin (AVP) neurones. As shown previously, exposure of hypothalamo-neurohypophyseal system explants to ATP and phenylephrine (PE) (alpha(1)-adrenergic agonist) causes a significantly larger increase in AVP release than with either agent alone and converts the response from a transient to a sustained stimulation of AVP release. Potential mechanisms for this synergism include presynaptic stimulation of excitatory afferent input (i.e. glutamate release), postsynaptic activation of receptors on AVP neurones, modulation of stimulus-secretion coupling in the neural lobe and/or involvement of glial/neuronal interactions. The response to ATP + PE (100 microM each) was not altered in the presence of either a cocktail of ionotropic glutamate receptor antagonists (CNQX + AP5) or a nonselective metabotropic glutamate receptor antagonist [(RS)-alpha-methyl-4-carboxyphenylglycine]. Thus, it is not dependent on activation of glutamate receptors. Treatment with tetrodotoxin (3 microM) eliminated the response to ATP + PE. Because this could reflect blockade of action potentials propagated from the AVP perikarya to the nerve terminals in the neural lobe or ...Continue Reading
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