Attempts to uncover subtypes of alpha-adrenoceptors and associated mechanisms by using sequential administration of blocking drugs.
By the sequential administration of alpha 1- and alpha 2-blockers it can be shown, in the pithed rabbit, that the dose/pressor response curve to noradrenaline consists of two separate curves, one for each receptor. alpha 2-mediated responses predominate at low doses and alpha 1-mediated responses predominate at high doses. Pressor responses to sympathetic nerve stimulation have, similarly, an alpha 2 component at low frequencies and a dominant alpha 1-mediated response at high frequencies: a residual response is resistant to combined alpha 1- plus alpha 2-blockade. This alpha-blocker-resistant pressor nerve response was further analysed in the pithed rat and was found to be partly susceptible to alpha,beta-methylene ATP, which desensitizes purinergic responses. However, reserpine pretreatment produced a greater reduction of nerve-mediated pressor responses than did alpha-blockade, suggesting that part of the 'alpha-blocker resistant' response might be adrenergic. It is concluded that sympathetic vasopressor nerve transmission is mediated for the greater part by alpha 1- and alpha 2-adrenoceptors but that there is evidence for contributions from non-alpha-adrenergic and 'purinergic' elements. An even greater proportion of the responses to circulating catecholamines is attributable to the alpha-receptors with a relatively small but significant 'resistant' component.
Grant
T L
TL
Flavahan
N A
NA
Greig
J
J
McGrath
J C
JC
McKean
C E
CE
Reid
J L
JL
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007093:Imidazoles; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000255:Adenosine Triphosphate; D011433:Propranolol; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D009638:Norepinephrine; D011224:Prazosin; C044484:Imiloxan