Low temperature prevents potentiation of norepinephrine release by phenylephrine.
The effect of 1-phenylephrine (1-PE), an alpha(1)-receptor agonist, was investigated on the release of tritiated norepinephrine ([3H]NE). Pairs of guinea pig vasa deferentia were loaded with [3H]NE, superfused continuously, and stimulated electrically. 1-PE (10, 100 microM) enhanced the basal release of tritium in concentration-dependent manner. The stimulation-evoked release of radioactivity was significantly increased by 100 microM 1-PE. Both basal and stimulation-evoked release by 1-PE were reduced by desipramine (10 microM), a monoamine uptake inhibitor. The effect of 1-PE on basal release was independent on extracellular Ca(2+) concentration ([Ca(2+)](o)) and alpha(1)-adrenoceptor blockade. However, the 1-PE-induced release was temperature dependent: at low temperature 1-PE failed to increase either basal or stimulation-evoked release of NE. Using three different temperatures (7, 12, 17 degrees C, respectively), it was found that basal release was blocked at all three temperature values but the stimulation-evoked release was inhibited only at the lower values. The effect of 1-PE on the NE release appears to involve a desipramine-, and temperature-sensitive process. These results suggest that a non-receptorial and direct carrier-mediated mechanism is involved in NE releasing effect of 1-PE.
Santha
E
E
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, PO Box 67, H-1450, Budapest, Hungary. santha@koki.hu
Lendvai
B
B
Gerevich
Z
Z
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003080:Cold Temperature; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010656:Phenylephrine; D002118:Calcium; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin