Evidence for tonic activation of prejunctional beta-adrenoceptors in guinea-pig pulmonary arteries by adrenaline derived from the adrenal medulla.
1. The effects of (+/-)-carteolol 10(-8) M to 10(-6) M, a non-selective beta-antagonist, applied cumulatively, on stimulation-evoked 3H-release at 1 Hz were studied in pulmonary arteries isolated from guinea-pigs. The guinea-pigs were subjected to either bilateral adrenalectomy, adrenalectomy followed by injections of deoxycorticosterone acetate (DOCA) and hydrocortisone, bilateral adrenodemedullation or a sham operation, and then loaded in vitro with [3H]-noradrenaline. 2. Carteolol inhibited 3H-output in arteries from sham-operated animals in a concentration-dependent manner. This inhibitory effect was not found in pulmonary arteries from animals subjected to adrenalectomy or adrenodemedullation. However, DOCA and hydrocortisone pretreatment, did not prevent the disappearance of the carteolol-induced inhibition of 3H-release. 3. Adrenalectomy and adrenodemedullation depleted or markedly reduced the endogenous contents of adrenaline in pulmonary arteries without altering the levels of dopamine and noradrenaline. 4. It is concluded that adrenaline, mainly derived from the adrenal medulla, acts as an endogenous agonist for tonically functioning prejunctional beta-adrenoceptors in guinea-pig pulmonary arteries, probably by being taken up and co-released with noradrenaline.
Misu
Y
Y
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Kuwahara
M
M
Amano
H
H
Kubo
T
T
D000313:Adrenal Medulla / Q000378:metabolism / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D002354:Carteolol; D002395:Catecholamines / Q000378:metabolism; D003900:Desoxycorticosterone / Q000494:pharmacology; D004837:Epinephrine / Q000096:biosynthesis / Q000494:pharmacology*; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000294:innervation; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D003900:Desoxycorticosterone; D002354:Carteolol; D006854:Hydrocortisone; D004837:Epinephrine