Release of endogenous noradrenaline from the vascularly perfused rat stomach in vitro: modulation by pre- and postsynaptic adrenoceptors.
We developed an experimental in vitro model to detect a very small amount of endogenous noradrenaline (NA) released from the rat gastric sympathetic nerve terminals. The stomach was perfused via celiac artery with modified Krebs-Ringer solution containing 10 mM pargyline and 0.1% bovine serum albumin at a constant flow of 4 ml/min. The right greater splanchnic (SPL) nerve (preganglionic nerve of the gastric sympathetic nerve) was stimulated electrically with square-wave pulses of 2 msec duration and supramaximal intensity (5 mA) for 1 min. The rat stomach contained about 750 ng of NA and spontaneous overflow was about 0.05% of tissue content per 2 min. The NA overflow induced by SPL nerve stimulation at 5 Hz was abolished by tetrodotoxin (3 x 10(-7) M) and by Ca(++)-free medium containing 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Hexamethonium (5 x 10(-4) M) significantly decreased the NA overflow induced by SPL nerve stimulation at 5 Hz. Yohimbine (10(-7) and 10(-6) M) and prazosin (10(-7) and 10(-6) M) dose-dependently enhanced the NA overflow induced by SPL nerve stimulation at 5 Hz. Clonidine (10(-7) and 10(-6) M) and methoxamine (10(-5) M) significantly decreased the NA overflow induced by SPL nerve stimulation at 1 Hz and this methoxamine-induced inhibition was abolished by 8-(p-sulfophenyl)-theophylline (5 x 10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Kochi Medical School, Japan.
K
K
Yokotani
Y
Y
Okuma
Y
Y
Osumi
D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000378:metabolism; D004558:Electric Stimulation; D005730:Ganglionic Blockers / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D013153:Splanchnic Nerves / Q000378:metabolism; D013270:Stomach / Q000098:blood supply / Q000187:drug effects / Q000294:innervation; D013779:Tetrodotoxin / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D011941:Receptors, Adrenergic; D002078:Butoxamine; D015016:Yohimbine; D018738:Hexamethonium; D013779:Tetrodotoxin; D008790:Metoprolol; D008729:Methoxamine; D007545:Isoproterenol; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin