Characterization of alpha-adrenoceptors in the vasculature of the canine nasal mucosa.
alpha-Adrenoceptors present in the vasculature of the nasal mucosa in beta-adrenoceptor blocked dogs have been characterized pharmacologically using selective alpha 1- and alpha 2-adrenoceptor agonists and antagonists. In pentobarbitone-anaesthetized dogs, intra-arterial (i.a.) administration of the selective alpha 1-agonists cirazoline and phenylephrine, the selective alpha 2-agonist UK-14,304 and the mixed alpha 1/alpha 2-agonists adrenaline, noradrenaline and oxymetazoline produced dose-related nasal vasoconstrictor responses (as measured by decreases in nasal cavity pressure). The rank order of agonist potency was adrenaline greater than oxymetazoline = UK-14,304 greater than noradrenaline greater than cirazoline greater than phenylephrine. The nasal response to cirazoline was inhibited by the selective alpha 1-adrenoceptor antagonist prazosin but not by the new, potent selective alpha 2-adrenoceptor antagonist RX811059. In contrast, UK-14,304 was inhibited only by RX811059. Either prazosin or RX811059 reduced the effect of the mixed agonist adrenaline. In spinal dogs, the noradrenaline-evoked fall in nasal cavity pressure was reduced by either prazosin or RX811059. Prazosin attenuated markedly the nasal vasoconstrictor response to electrical stimulation of postganglionic fibres emerging from the superior cervical ganglion (SNS) whereas RX811059 was ineffective. Administration of the neuronal re-uptake inhibitor cocaine potentiated the effect of i.a. noradrenaline but reduced marginally the maximal response to SNS. After cocaine, RX811059 enhanced the effect of SNS and attenuated the response to noradrenaline. Prazosin reduced effectively the responses to both SNS and noradrenaline after cocaine. Pretreatment with the alpha 2-agonist UK-14,304 did not affect the response to noradrenaline in the nasal cavity but evoked a persistent (up to 2 h) reduction in the response to SNS. RX811059 antagonized the inhibitory effect of UK-14,304. These results demonstrate that both postjunctional alpha 1- and alpha 2-adrenoceptors mediating vasoconstriction are present in the canine nasal mucosa. In addition, sympathetic neurones innervating the nasal mucosa are characterized by a very efficient re-uptake process and contain prejunctional alpha 2-adrenoceptors.
Berridge
T L
TL
Roach
A G
AG
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D003655:Decerebrate State; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D008297:Male; D009297:Nasal Mucosa / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D010726:Phosphodiesterase Inhibitors; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D009638:Norepinephrine