Pharmacological analysis of neurogenic, sympathetic responses mediated through alpha-1-, alpha-2-adrenergic and purinergic receptors in the dog saphenous vein.
Electrical transmural stimulation evoked a sympathetic contraction in the isolated dog saphenous vein. This contraction consisted of three components (alpha(1)-adrenergic, alpha(2)-adrenergic and purinergic), which were separately observed under combined treatments either with yohimbine (blockade of alpha(2)-adrenoceptor) and alpha,beta-methylene ATP (desensitization of P(2X)-purinoceptors), with prazosin (blockade of alpha(1)-adrenoceptor) and alpha,beta-methylene ATP, or with prazosin and yohimbine, respectively. The alpha(1)-adrenergic and purinergic contractions immediately developed after the start of stimulation and reached a peak rapidly. In contrast, the alpha(2)-adrenergic contraction developed slowly, thus the time to peak contraction was longer than the other two components. The relationship between the peak amplitudes of contraction and stimulus frequencies were similar between alpha(1)- and alpha(2)-adrenergic components, but the purinergic contraction was smaller than the other components at all frequencies (0.1-30 Hz). Cocaine, a neuronal uptake inhibitor of noradrenaline, significantly potentiated alpha(1)- and alpha(2)-adrenergic components and prolonged their duration with a relatively greater effect on the alpha(2)-adrenergic component. In contrast, the purinergic component was not affected by cocaine. Exogenous noradrenaline produced concentration-dependent contraction, which was inhibited more effectively after combined treatment with combination of prazosin and yohimbine than either blocker given alone. Cocaine potentiated the attenuated contractile response to noradrenaline in the presence of prazosin, resulting in the recovery of response to the control level. Exogenous ATP produced a transient contraction, which was abolished under conditions where postjunctional P(2X)-purinoceptors were desensitized with alpha,beta-methylene ATP. Cocaine did not affect the ATP-induced contraction. These results suggest that sympathetic contraction of the dog saphenous vein is caused through three distinct routes (alpha(1)- and alpha(2)-adrenoceptors and P(2X)-purinoceptors).
Hiraoka
Y
Y
Department of Pharmacology, School of Medicine, Fukui Medical University, Matsuoka, Fukui, Japan.
Taniguchi
T
T
Oshita
M
M
Muramatsu
I
I
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000502:physiology; D012501:Saphenous Vein / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011983:Receptors, Purinergic; D015016:Yohimbine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine; D011224:Prazosin