Distribution of substance P receptors in rabbit airways, functional and autoradiographic studies.
We have studied systematically the distribution of receptors for substance P in the airway smooth muscle of the rabbit using both functional studies and light-microscopic autoradiography. Four areas of the respiratory tract were examined: the midtrachea (T1) and proximal, middle and distal portions of the right main bronchus (B1, B2 and B3, respectively). The magnitude of the contractile response to substance P in preparations from six to eight animals was location-dependent, increasing significantly from proximal to distal areas. Maximal tension expressed as a function of tissue weight +/- S.E.M. was 24.8 +/- 3 for T1, 39 +/- 10 for B1, 108 +/- 31 for B2 and 160 +/- 42 for B3. The potency of substance P in B2 and B3 was significantly greater (EC50 = 4.8 x 10(-7) M; 2.8 x 10(-7) M, respectively) than that in T1 (2.5 x 10(-6) M). After inhibition of endogenous enkephalinase by phosphoramidon there was an increase in sensitivity to substance P in both T1 (EC50 = 2.3 x 10(-7) M, n = 5) and B3 (2.6 x 10(-9) M, n = 5). There was remarkable agreement in the results obtained with autoradiography. No binding sites (0) were visualized to Bolton Hunter substance P in T1. Sparse but specific binding (+) was seen in B1, whereas it was marked ( ) in B2 and very dense ( ++) in B3. Thus, our results have shown that receptors for substance P are more numerous in the distal than proximal airways of the rabbit. This may indicate a physiological role for substance P in the regulation of airway smooth muscle tone in the distal airways.
Department of Pharmacology, University of Sydney, New South Wales, Australia.
J
J
Black
L
L
Diment
C
C
Armour
L
L
Alouan
P
P
Johnson
D000818:Animals; D001345:Autoradiography; D001980:Bronchi / Q000032:analysis* / Q000187:drug effects / Q000502:physiology; D006020:Glycopeptides / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D011817:Rabbits; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000032:analysis*; D013373:Substance P / Q000494:pharmacology; D014132:Trachea / Q000032:analysis* / Q000187:drug effects / Q000502:physiology
D006020:Glycopeptides; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; C008890:phosphoramidon