Neuronally released (-)-noradrenaline relaxes smooth muscle of calf trachea mainly through beta 1-adrenoceptors: comparison with (-)-adrenaline and relation to adenylate cyclase stimulation.
The nature of the receptors that mediate the relaxation of smooth muscle by field stimulation, (-)-noradrenaline and (-)-adrenaline was investigated in calf tracheal smooth muscle. The relation between relaxation, stimulation of the adenylate cyclase and density of beta-adrenoceptor subtypes was studied with the help of antagonists of beta 1- and beta 2-adrenoceptors. The question of the existence of catecholamine-containing nerves was also investigated. (1) Nerves with varicosities exhibiting catecholaminergic fluorescence were observed between bundles of smooth muscle cells. (2) Consistent with the existence of adrenergic nerves (-)-noradrenaline was also found. The content of (-)-noradrenaline (1 microgram.g-1 w.w.) was the same in smooth muscle strips from the sublaryngeal region and from the region close to the bifurcation of the calf trachea. (-)-Adrenaline was not detected. (3) Smooth muscle relaxation by low (-)-noradrenaline concentration (0.6-2 nmol/l) was mediated through beta 1-adrenoceptors. Low concentrations of (-)-adrenaline (0.06-1 nmol/l) relaxed through beta 2-adrenoceptors. High concentrations of (-)-noradrenaline and (-)-adrenaline also caused relaxation through beta 2- and beta 1-adrenoceptors respectively. (4) Field stimulation caused relaxation which was half maximal at 0.2-0.8 Hz. Blockade of beta 1-adrenoceptors strongly attenuated the relaxant response to field stimulation and shifted the frequency-relaxation curves to 4 times higher frequencies. These results are consistent with a beta 1-adrenoceptor-mediated relaxation caused by (-)-noradrenaline released from sympathetic nerve endings at low stimulation frequencies. (5) Blockade of beta 2-adrenoceptors failed to reduce smooth muscle relaxation caused by field stimulation at low stimulation frequencies (0.1-1 Hz). However, after beta 1-adrenoceptor blockade, additional blockade of beta 2-adrenoceptors reduced the relaxant effects observed at high frequencies (2-400 Hz). The results suggest that high concentrations of endogenous (-)-noradrenaline cause relaxation through beta 2-adrenoceptors. (6) Binding experiments with 3H-(-)-bupranolol and 3H-ICI 118,551 revealed between 10,000 and 20,000 beta-adrenoceptors per smooth muscle cell of which 3/4 were beta 2 and 1/4 beta 1. The equilibrium dissociation constant of (-)-adrenaline for both beta 1- and beta 2-adrenoceptors and of (-)-noradrenaline for beta 1-adrenoceptors was 1 mumol/l. The affinity of (-)-noradrenaline for beta 2-adrenoceptors was 10 to 20 times lower than for beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Lemonine
H
H
Department of Clinical Physiology, University of Düsseldorf, Federal Republic of Germany.
Novotny
G E
GE
Kaumann
A J
AJ
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology / Q000502:physiology; D002417:Cattle; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000201:enzymology / Q000502:physiology*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism* / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014132:Trachea / Q000201:enzymology / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D007093:Imidazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; C049763:CGP 20712A; D000262:Adenylyl Cyclases; D009638:Norepinephrine; D004837:Epinephrine