Adrenergic and purinergic cotransmission in nicotine-evoked vasoconstriction in rabbit ileocolic arteries.
The possible involvement of ATP, in addition to noradrenaline, in nicotine-evoked vasoconstriction was studied in branches of the ileocolic artery of the rabbit. For measurement of vasoconstrictor responses, the arteries were simultaneously incubated and perfused. For measurement of the release of [3H]-noradrenaline, they were preincubated with [3H]-noradrenaline and then superfused. Prazosin (0.1 mumol/l) antagonized the constrictor effect of exogenous noradrenaline but not that of exogenous ATP. Desensitization of P2X-receptors by alpha, beta-methylene ATP markedly attenuated the effect of exogenous ATP but not that of noradrenaline. The presumed P2-purinoceptor antagonist suramin (100 mumol/l) reduced the maximal contraction obtainable with noradrenaline and shifted the concentration-response curve for the constrictor effect of alpha, beta-methylene ATP to the right, but did not change the effect of ATP. Nicotine elicited monophasic vasoconstrictions which faded while nicotine was still in the medium. The concentration-response curve was bell-shaped with an EC50 of 50 mumol/l and a maximal effect at 180 mumol/l, and the exposure time-response curve indicated that responses were maximal after 5 s of contact of nicotine (180 mumol/l) with the tissue. Neither prazosin 0.1 mumol/l nor desensitization by alpha,beta-methylene ATP changed the time course of the response to nicotine, but both depressed the magnitude of the responses over the whole concentration- and exposure time-response curves. The depression was greater with prazosin than with alpha,beta-methylene ATP. Desensitization by alpha,beta-methylene ATP or addition of suramin 100 mumol/l practically abolished the prazosin-resistant part of the response. The effect of nicotine was blocked by hexamethonium as well as by sympathetic denervation by 6-hydroxydopamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Bültmann
R
R
Pharmakologisches Institut, Freiburg, Federal Republic of Germany.
von Kügelgen
I
I
Starke
K
K
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000098:blood supply; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D011978:Receptors, Nicotinic; D013498:Suramin; D009538:Nicotine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine; D011224:Prazosin