Adenosine 5'-triphosphate and neuropeptide Y are co-transmitters in conjunction with noradrenaline in the human saphenous vein.
1. Human saphenous veins were used to assess the cooperative participation of adenosine 5-triphosphate (ATP), neuropeptide Y (NPY), and noradrenaline (NA) in the vasomotor responses elicited following electrical depolarization of the perivascular nerve terminals. Rings from recently dissected human biopsies were mounted to record isometric muscular contractions; the motor activity elicited in the circular muscle layer following electrical depolarization (2.5-20 Hz, 50 V, 0.5 msec) were recorded. 2. Incubation of the biopsies with either 100 nM tetrodotoxin (TTX) or 1 microM guanethidine abolished the vasomotor response elicited by electrical nerve depolarization. The independent application of either ATP or NA to vein rings induced concentration-dependent contractions. 3. Tissue incubation with 30 microM suramin or 10 nM prazosin produced 10 fold rightward displacements of the alpha,beta-methylene ATP and NA concentration-response curves respectively. NPY contracted a limited number of biopsies, the vasoconstriction elicited was completely blocked by 1 microM BIBP 3226. A 5 min incubation of the biopsies with 10-100 nM NPY synergized, in a concentration-dependent fashion, both the ATP and the ATP analogue-induced contractions. Likewise, tissue preincubation with 10 nM NPY potentiated the vasomotor responses evoked with 20-60 nM NA. 4. Neither suramin, BIBP 3226, nor prazosin was individually able to significantly modify the derived frequency-tension curves. In contrast, the co-application of 30 microM suramin and 10 nM prazosin or 30 microM suramin and 1 microM BIBP 3226, elicited a significant (P<0.01) downward displacement of the respective frequency-tension curves. 5. The simultaneous application of the three antagonists-30 microM suramin, 1 microM BIBP 3226 and 10 nM prazosin-caused a significantly greater displacement of the frequency-tension curve than that achieved in experiments using two of these antagonists. 6. Electrically-evoked vasomotor activity is blocked to a larger extent by tissue incubation with 2.5 microM chloroethylclonidine and 30 microM suramin rather than with 10 nM 5 methyl urapidil and 30 microM suramin. As a result, the alpha1-adrenoceptor involved in the vasomotor activity has tentatively been associated with the alpha1B adrenoceptor family subtype. 7. Results support the physiological role of ATP in sympathetic neurotransmission. The present results are consistent with the working hypothesis that human sympathetic vasomotor reflexes involve the coordinated motor action of ATP, NPY, and NA acting on vascular smooth muscle cells. The present results support the concept of sympathetic co-transmission in the human saphenous vein.
Racchi
H
H
Departamento de Fisiología, Escuela de Medicina, P. Universidad Católica de Chile, Santiago.
Irarrázabal
M J
MJ
Howard
M
M
Morán
S
S
Zalaquett
R
R
Huidobro-Toro
J P
JP
D000255:Adenosine Triphosphate / Q000502:physiology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009478:Neuropeptide Y / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D011224:Prazosin / Q000494:pharmacology; D058914:Purinergic Antagonists; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D014151:Anti-Anxiety Agents; C092926:BIBP 3226; D009478:Neuropeptide Y; D018377:Neurotransmitter Agents; D058914:Purinergic Antagonists; D017476:Receptors, Neuropeptide Y; D011983:Receptors, Purinergic; D013498:Suramin; D000255:Adenosine Triphosphate; D001120:Arginine; D009638:Norepinephrine; D011224:Prazosin