Contraction-mediating alpha 2-adrenoceptors in the mouse vas deferens.
The question of the existence of postjunctional, contraction-mediating alpha 2-adrenoceptors, in addition to the known alpha 1-adrenoceptors, was studied in the mouse isolated vas deferens. Both the alpha 1-selective agonist phenylephrine and the alpha 2-selective agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) caused contraction of the vas deferens. In the presence of the alpha 1-selective antagonist prazosin (added in order to prevent an alpha 1 component in the effect of high concentrations of UK 14,304), the alpha 2-selective antagonist yohimbine and idazoxan shifted the concentration-response curve of UK 14,304 to the right in a manner compatible with competitive antagonism and with dissociation constants KB indicating the involvement of alpha 2-adrenoceptors. The maximal contraction elicited by UK 14,304 (in the presence of prazosin) was much lower than the maximal contraction elicited by phenylephrine. The effect of UK 14,304 was not changed by the P2-purinoceptor agonist alpha,beta-methylene-ATP and was reduced by neuropeptide Y, but was markedly enhanced by relatively low concentrations of phenylephrine. When the sympathetic fibres of the vas deferens were stimulated by trains of ten widely spaced (0.5 Hz) electric pulses, the tissue responded with ten separate twitches in which purinergic and adrenergic components were isolated by prazosin and suramin, respectively. Prazosin reduced the first adrenergic twitch in these trains at concentrations close to its KB value at alpha 1-adrenoceptors, whereas yohimbine and idazoxan reduced the first adrenergic twitch at concentrations far lower than their KB values at alpha 1-adrenoceptors.(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 / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000494:pharmacology; D004347:Drug Interactions; D019329:Idazoxan; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009478:Neuropeptide Y / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011810:Quinoxalines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism / Q000502:physiology; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D009478:Neuropeptide Y; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D013498:Suramin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D011224:Prazosin; D019329:Idazoxan