Somatostatin inhibits the release of noradrenaline induced by electrical stimulation of the rat mesenteric artery.
Somatostatin, a peptide with antisecretory and antiproliferative effects, coexists with noradrenaline in sympathetic neurons. Octreotide, a stable somatostatin analogue, prevents hypertension and cardiovascular structural changes induced by prolonged infusion of DPSPX (1,3-dipropyl-8-sulfophenylxanthine, a non-selective adenosine receptor antagonist) in rats. In the present work we investigated the effect of somatostatin and its analogue octreotide on the release of [(3)H]noradrenaline from sympathetic nerves in the rat mesenteric artery. Rat mesenteric arteries were incubated for 60 min with [(3)H]noradrenaline (0.2 microm), mounted in perifusion chambers, washed out for 90 min and electrically stimulated (2 Hz, 5 min, 50 mA). Radioactivity was measured in the tissue and in the perifusion fluid before, during and after stimulation. Both somatostatin and octreotide inhibited tritium release evoked by electrical stimulation of in vitro preparations of rat mesenteric arteries preloaded with [(3)H]noradrenaline. The maximal effects produced by octreotide and somatostatin were a 56 and 70% inhibition of noradrenaline release, respectively. For somatostatin an EC(50)=0. 18 n m (0.01 n m-2.2 n m;n =16) was calculated. When used alone, the somatostatin receptor antagonist, cyclo(7-aminoheptanoyl-Phe- d -Trp-Lys-Thr[BZL]) (CYCAM; 1 microm), had no effect on noradrenaline release induced by electrical stimulation. However, it was able to significantly antagonize the inhibitory effects of octreotide and somatostatin. These results are compatible with a negative modulatory role of somatostatin on sympathetic neurotransmission.
Calhau
C
C
Faculty of Medicine, Institute of Pharmacology and Therapeutics, Porto, 4200, Portugal.
Martel
F
F
Moura
D
D
Azevedo
I
I
D000818:Animals; D004558:Electric Stimulation; D006727:Hormone Antagonists / Q000494:pharmacology*; D006728:Hormones / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D015282:Octreotide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D006727:Hormone Antagonists; D006728:Hormones; D013004:Somatostatin; C043820:cyclo(7-aminoheptanoylphenylalanyl-tryptophyl-lysyl-benzylthreonyl); D015282:Octreotide; D009638:Norepinephrine