title: Comparison between sympathetic adrenergic and purinergic transmission in the dog mesenteric artery.
abstract: 1. Electrical transmural stimulation evoked a sympathetic contraction in the isolated dog mesenteric artery. This contraction consisted of adrenergic and purinergic components, which were separately observed under conditions where postjunctional P2 purinoceptors were desensitized with alpha, beta-methylene ATP or postjunctional alpha 1 adrenoceptors were blocked by prazosin, respectively. 2. The purinergic component was transient and developed immediately after the start of stimulation and declined rapidly after a peak. In contrast, the adrenergic contraction slowly developed and lasted longer than the purinergic component. Thus, the purinergic and adrenergic components predominantly contributed to the early and later phases of the total sympathetic response, respectively. 3. The peak amplitudes of contraction of both components were similar at 1 Hz, but the adrenergic component occurred more dominantly in the responses to higher frequency stimulation. 4. Cocaine, a neuronal uptake inhibitor of noradrenaline, potentiated the adrenergic component but attenuated the purinergic component. This attenuation was reversed by DG-5128, a prejunctional alpha 2 adrenoceptor antagonist. Treatment with DG-5128 alone augmented both adrenergic and purinergic components. 5. 8-Phenyltheophylline, a P1 purinoceptor antagonist, potentiated the purinergic component without affecting the adrenergic component. 6. Exogenous noradrenaline produced a sustained contraction, which was potentiated by cocaine and was competitively inhibited by prazosin. alpha, beta-Methylene ATP and 8-phenyltheophylline had no effect on the response to noradrenaline. Exogenous ATP produced a transient contraction, which was abolished under conditions where postjunctional P2 purinoceptors were desensitized with alpha, beta-methylene ATP. 8-Phenyltheophylline potentiated but cocaine or prazosin did not affect the ATP response. 7. Electrical stimulation produced an increase in 3H efflux from the sympathetic nerve terminals in the mesenteric arteries pre-incubated with [3H]noradrenaline. The evoked efflux was significantly augmented by cocaine or DG-5128 and was inhibited by guanethidine or tetrodotoxin. alpha, beta-Methylene ATP and 8-phenyltheophylline were without effect. Adenosine reduced the 3H efflux and the inhibition was suppressed by 8-phenyltheophylline. 8. These results suggest that sympathetic contraction of the dog mesenteric artery is caused through not only adrenergic but also purinergic mechanisms, and that both the sympathetic transmissions are predominantly modulated through prejunctional adrenergic mechanisms.
authors.affiliation: Department of Pharmacology, Fukui Medical School, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Muramatsu
authors.forename: T
authors.initials: T
authors.lastname: Ohmura
authors.forename: M
authors.initials: M
authors.lastname: Oshita
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D007093:Imidazoles; D011941:Receptors, Adrenergic; D011983:Receptors, Purinergic; C032368:midaglizole; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D003042:Cocaine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine; D011224:Prazosin