Article date: May 1993
By: A. Butler, S.P. Worton, C.T. O'Shaughnessy, H.E. Connor, in Volume 109, Issue 1, pages 126-130
Effects of the α2‐adrenoceptor agonists, UK14304 and clonidine, the 5‐HT1 receptor agonist, sumatriptan and the κ‐opioid receptor agonist, GR103545, on sensory neurotransmission in histamine‐contracted guinea‐pig isolated pulmonary artery (GPPA) have been studied.
Electrical field stimulation (EFS) induced frequency‐dependent relaxations of histamine‐contracted GPPA, which were attenuated by tetrodotoxin and capsaicin pretreatment but not by the nitric oxide synthase inhibitor, Nω‐nitro‐l‐arginine methyl ester (l‐NAME).
Substance P (0.3 μm) induced relaxations which were subject to rapid tachyphylaxis. Neither the NK1 receptor antagonist, (±)‐CP 96,345, nor desensitization to substance P had any effect of EFS‐induced relaxations of histamine‐contracted GPPA.
Calcitonin gene‐related peptide (CGRP; 3 and 30 nm) induced concentration‐dependent relaxations of histamine‐contracted GPPA. The putative CGRP receptor antagonist, CGRP8–37 (1 μm), markedly attenuated EFS‐induced relaxations as well as relaxations induced by a low concentration of CGRP.
Sumatriptan (0.1 and 1 μm) and the selective K‐opioid receptor agonist, GR103545 (10 and 100 nm) had no effect on EFS‐induced relaxations of histamine‐contracted GPPA. In contrast, the α2‐adrenoceptor agonists UK14304 (1–100 nm) and clonidine (300 nm) attenuated responses to EFS, the attenuation of UK14304 (100 nm) being reversed by yohimbine (300 nm).
It is concluded that in GPPA, where a presynaptic inhibition of sensory neurotransmission by α2‐adrenoceptor activation could be shown, there was no evidence for such modulation by either sumatriptan‐sensitive 5‐HT1 receptors or κ‐opioid receptors.
Effects of the α2‐adrenoceptor agonists, UK14304 and clonidine, the 5‐HT1 receptor agonist, sumatriptan and the κ‐opioid receptor agonist, GR103545, on sensory neurotransmission in histamine‐contracted guinea‐pig isolated pulmonary artery (GPPA) have been studied.
Electrical field stimulation (EFS) induced frequency‐dependent relaxations of histamine‐contracted GPPA, which were attenuated by tetrodotoxin and capsaicin pretreatment but not by the nitric oxide synthase inhibitor, Nω‐nitro‐l‐arginine methyl ester (l‐NAME).
Substance P (0.3 μm) induced relaxations which were subject to rapid tachyphylaxis. Neither the NK1 receptor antagonist, (±)‐CP 96,345, nor desensitization to substance P had any effect of EFS‐induced relaxations of histamine‐contracted GPPA.
Calcitonin gene‐related peptide (CGRP; 3 and 30 nm) induced concentration‐dependent relaxations of histamine‐contracted GPPA. The putative CGRP receptor antagonist, CGRP8–37 (1 μm), markedly attenuated EFS‐induced relaxations as well as relaxations induced by a low concentration of CGRP.
Sumatriptan (0.1 and 1 μm) and the selective K‐opioid receptor agonist, GR103545 (10 and 100 nm) had no effect on EFS‐induced relaxations of histamine‐contracted GPPA. In contrast, the α2‐adrenoceptor agonists UK14304 (1–100 nm) and clonidine (300 nm) attenuated responses to EFS, the attenuation of UK14304 (100 nm) being reversed by yohimbine (300 nm).
It is concluded that in GPPA, where a presynaptic inhibition of sensory neurotransmission by α2‐adrenoceptor activation could be shown, there was no evidence for such modulation by either sumatriptan‐sensitive 5‐HT1 receptors or κ‐opioid receptors.
DOI: 10.1111/j.1476-5381.1993.tb13541.x
View this article