Evidence for the existence of ‘atypical’β‐adrenoceptors (β₃‐adrenoceptors) mediating relaxation in the rat distal colon in vitro

Abstract

Responses to BRL 37344 in the presence of phentolamine (1puM) and propranolol (1 pM) were antagonized by (±)-cyanopindolol (IpM), with an apparent pA2 value of 6.67. Responses to isoprenaline, under the same conditions, were antagonized in a competitive manner by (±)-cyanopindolol (0.1 to 10pM), with the slope of the Schild plot close to unity and a pA2 value of 7.12. 6 The resistance of the relaxant responses to antagonism by phentolamine and propranolol, along with the relatively high potency of the #3-adrenoceptor agonist BRL 37344 and the antagonism of 'resistant' responses by (±)-cyanopindolol would suggest that 'atypical' f6-adrenoceptors, similar to the fl3-adrenoceptors of rat adipocytes and other tissues, exist in the rat distal colon.

Characterization of catecholamine‐mediated relaxations in rat isolated gastric fundus: evidence for an atypical β‐adrenoceptor

“…The pKB of 6.3, calculated from the single (1 pM) concentration of propranolol, is low compared with 8.2-8.8 for classical f1-adrenoceptors mediating atrial stimulation and 8.3-8.6 for #2-adrenoceptors mediating tracheal relaxation suggesting an action at atypical aadrenoceptors. A similarly low pKB was reported for propranolol at atypical fl-adrenoceptors mediating lipolysis (6.6, Wilson et al, 1984) or relaxation in rat distal colon (6.57, McLaughlin & MacDonald, 1990b).…”

“…However, relaxant responses to catecholamines which are resistant to blockade by a-and f-adrenoceptor antagonists have also been reported in a number of gastrointestinal smooth muscle preparations including rabbit stomach (Bristow et al, 1970), rabbit colon (Gillespie & Khoyi, 1977), rat oesophageal smooth muscle (Buckner & Christopherson, 1974), guinea-pig ileum (Wikberg, 1977;Bond et al, 1986;Bond & Clarke, 1987), dog colon (Grivegnee et al, 1984), rat gastric fundus (Dettmar et al, 1986;McLaughlin & MacDonald, 1990a;, rat proximal colon (Croci et al, 1988;Manara et al, 1989;Bianchetti & Manara, 1990), rabbit jejunum (Norman & Leathard, 1990), rat jejunum (Van der Vliet et al, 1990) and rat distal colon (McLaughlin & MacDonald, 1989;1990b). In the guinea-pig ileum, the order and relative potency of catecholamines is consistent with /3-adrenoceptors although responses were resistant to propranolol (Bond & Clarke, 1988).…”

“…In addition, the receptor mediating propranololresistant responses is characterized by the relatively high potency of a novel class of /J-adrenoceptor agonists , e.g. BRL 37344 in guinea-pig ileum (Bond & Clarke, 1988) and rat distal colon (McLaughlin & MacDonald, 1990b) and BRL 35135 in guinea-pig gastric fundus (Coleman et al, 1987).…”

Adrenoceptors mediating relaxation to catecholamines in rat isolated jejunum

“…Bond & Clarke (1988) further experiments to analyse these small shifts further but it seems likely that they were produced by blockade of classical P-adrenoceptors since (i) propranolol itself has been shown to produce similar shifts in rat colon and fundus (McLaughlin & MacDonald, 1990; and (ii) o-adrenoceptor mediated inhibitory effects in smooth muscle involve abolition of spontaneous spike discharge and hyperpolarization (Bulbring, 1954;1957) and are not seen if the tissue is depolarized sufficiently to block spike generation (Magaribuchi & Kuriyama, 1972). The relative potencies of the catecholamines and BRL 37344 in the presence of prazosin and propranolol, with BRL 37344 becoming more potent than isoprenaline, are similar to those obtained by Bond & Clarke (1988) at the atypical P-adrenoceptors in guinea-pig ileum.…”

“…In addition, it has been reported that the non-selective P-adrenoceptor antagonist, cyanopindolol (Engel et al, 1981) is a competitive and relatively potent antagonist at atypical P-adrenoceptors in the gut (Blue et al, 1989;McLaughlin & MacDonald, 1990; and therefore the effect of cyanopindolol on responses to adrenaline was investigated.…”