Neuropeptide Y potentiates noradrenaline-evoked vasoconstriction by an intracellular calcium-dependent mechanism.
The potentiating effect of neuropeptide Y (NPY) was examined by testing the influence of putative inhibitors of calcium entry on the NPY-enhanced contractile response to noradrenaline in the guinea pig uterine artery. In order to examine the involvement of voltage sensitive calcium entry mechanisms we recorded the effect of noradrenaline and NPY on the membrane potential. NPY (100-300 nM) enhanced noradrenaline-evoked vasoconstriction. The potentiation by NPY was most prominent in low noradrenaline concentrations (30-300 nM) and the pD10 (-log molar concentration of agonist eliciting 10% of maximum contraction) value was increased from 6.43 +/- 0.07 to 6.97 +/- 0.11 (P < 0.001, n = 6). Inhibition of extracellular calcium influx shifted concentration-dependently to the right the concentration-response curve for noradrenaline but potentiation by NPY still remained. The intracellular calcium chelator quin-2 AM selectively abolished the NPY-induced enhancement of the contractile response to noradrenaline. In contrast, quin-2 AM (10-30 microM) had no inhibitory effect on the contractile response to noradrenaline per se. It is suggested that NPY initiates an intracellular calcium-sensitive mechanism which increase alpha-adrenoceptor sensitivity. This results in a significant increase of sarcoplasmic calcium and stronger contractile responses to noradrenaline.
Fallgren
B
B
Perstorp Pharma, Research and Development, Science Park IDEON, Lund, Sweden.
Arlock
P
P
Edvinsson
L
L
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002614:Chelating Agents; D009478:Neuropeptide Y; D014700:Verapamil; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine