Sustained prejunctional facilitation of noradrenergic neurotransmission by adrenaline as a co-transmitter in the portal vein of freely moving rats.
1. The duration of the facilitatory effect of adrenaline on the electrically evoked overflow of noradrenaline was studied in the portal vein of permanently adreno-demedullated freely moving rats. 2. Rats were infused with adrenaline (20 or 100 ng min-1) for 2 h. After an interval of 1 h, when plasma adrenaline had returned to undetectable levels, electrical stimulation resulted in an enhanced catecholamine overflow amounting to 219% (noradrenaline) and 241% (noradrenaline plus adrenaline) of control (saline infusion), respectively. 3. When stimulation was applied again, in the same animal, at 24, 48 and 72 h after the first stimulation episode, the evoked noradrenaline overflow was 150, 111 and 102% (after 20 ng ml-1 adrenaline) and 158, 134 and 105% (after 100 ng min-1 adrenaline) of control. 4. The beta 2-adrenoceptor antagonist, ICI 118,551 (0.3 mg kg-1), blocked the facilitatory effect obtained after the 100 ng min-1 adrenaline infusion on all days. 5. The results show that adrenaline, after being taken up by and released from sympathetic nerve terminals, is able to facilitate the evoked noradrenaline overflow through activation of prejunctional beta 2-adrenoceptors for at least 48 h after administration.
Department of Medicinal Chemistry and Molecular Pharmacology, University of Groningen, The Netherlands.
R P
RP
Coppes
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F
Brouwer
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I
Freie
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J
Smit
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J
Zaagsma
D000313:Adrenal Medulla / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000494:pharmacology*; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D011169:Portal Vein / Q000187:drug effects / Q000294:innervation*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D015306:Biogenic Monoamines; D011412:Propanolamines; C026777:ICI 118551; D009638:Norepinephrine; D004837:Epinephrine