Antagonism of pre- and postjunctional responses to neuropeptide Y and sympathetic stimulation by D-myo-inositol-1,2,6-trisphosphate in the anaesthetised dog.
Pre- and postjunctional responses to nerve released or exogenous neuropeptide Y (NPY) were measured in the anaesthetised dog before and after administration of D-myo-inositol-1,2,6-trisphosphate (PP56) a putative NPY antagonist. The inhibition of the increase in pulse interval evoked by vagal stimulation was used as a measure of prejunctional action of NPY and the magnitude of increase in blood pressure was used as a measure of postjunctional action of NPY (direct action or constrictor potentiating). Elevated plasma levels of PP56 were maintained throughout the course of the experiment. PP56 significantly reversed the inhibitory effect of NPY (nerve released or exogenous) on cardiac vagal action, and significantly inhibited the pressor response to exogenous NPY. PP56 did not affect the pressor response to intravenous phenylephrine, a selective alpha-adrenoceptor agonist. PP56 therefore significantly antagonises both pre- and postjunctional effects of NPY (nerve released and exogenous) and, with respect to its postjunctional antagonism, this action is selective for NPY.
Potter
E K
EK
School of Physiology and Pharmacology, University of New South Wales, Kensington, Sydney, Australia.
Edvinsson
L
L
Gustafsson
T
T
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D007295:Inositol Phosphates / Q000097:blood / Q000494:pharmacology*; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D007295:Inositol Phosphates; D009478:Neuropeptide Y; D010656:Phenylephrine; C059368:atrinositol