Inhibition of rat colon motility by stimulation of atypical beta-adrenoceptors with new gut-specific agents

Croci, Tiziano; Cecchi, Roberto; Tarantino, A; Aureggi, Giulio; Bianchetti, A.; Boigegrain, Robert; Manara, L.

doi:10.1016/s0031-6989(88)80007-9

Cited by 31 publications

(27 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…That is, the putative adrenoceptor is resistant to propranolol at concentrations that are at least 8 to 16 times its equilibrium dissociation constant for the adipocyte receptor. A 1 log unit difference between equilibrium dissociation constants for an antagonist may be taken as strong evidence for distinct sites (Furchgott, 1972;Eglen & Whiting, 1987 There are several other examples in the literature of fi-adrenoceptor-like responses to phenylethylamine based agonists which are resistant to a-and P-adrenoceptor blockade (Morris et al, 1981;Drew & Hilditch, 1984;Broadley et al, 1985;Bentley & Starr, 1986;Dettmar et al, 1986;Croci et al, 1988). The study by Croci et al (1988) is especially noteworthy in that these authors appear to have identified a putative #-adrenoceptor subtype in rat colon which is stimulated selectively by a series of novel agonists (phenylethanolaminotetralines).…”

Section: Discussionmentioning

confidence: 99%

Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the α‐ and β‐subtypes

Bond

Clarke

1988

British J Pharmacology

151

View full text Add to dashboard Cite

1 Experiments were done to characterize a putative adrenoceptor which functions to inhibit longitudinal muscle tension development in the guinea-pig ileum. Several (0.27). 4 The resistance to blockade by propranolol (5 pM), the low affinity of nadolol, and the order and relative potency of agonists, suggest the presence of an adrenoceptor with distinct pharmacological characteristics from currently defined a-and P-adrenoceptors.

show abstract

Section: Discussionmentioning

confidence: 99%

Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the α‐ and β‐subtypes

Bond

Clarke

1988

British J Pharmacology

151

View full text Add to dashboard Cite

show abstract

“…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).…”

Section: Introductionmentioning

confidence: 90%

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

McLaughlin

MacDonald

1991

British J Pharmacology

View full text Add to dashboard Cite

1 Experiments were carried out in order to characterize the receptors mediating relaxant responses to catecholamines in the rat gastric fundus. The effects of noradrenaline, isoprenaline and the 'atypical' or 13-adrenoceptor agonist, BRL 37344, on methacholine-induced tone were measured. Prazosin, propranolol and cyanopindolol were used as antagonists. 2 Relaxant responses to noradrenaline, in the presence of propranolol (1 M) were antagonized in a concentration-dependent manner by prazosin (0.01 to 1,pM), although this antagonism was weak and non-competitive in nature. Relaxant responses to isoprenaline, in the presence of prazosin (0.1 ,UM), were antagonized only by the highest concentration of propranolol (1 pM) giving a pKB of 6.3. BRL 37344 also relaxed the rat gastric fundus in the presence of prazosin (0.1 pM), and the responses to BRL 37344 were unaffected by propranolol (1 pM). 3 Tachyphylaxis to BRL 37344 was observed, a second concentration-response curve being significantly shifted to the right. Exposure of tissues to BRL 37344 (1 pM) between concentration-response curves also caused an 11 fold rightward shift in the response to isoprenaline. 4 In the presence of prazosin (0.1 uM) and propranolol (1,UM), the rank order of potency of the agonists was: (-)-isoprenaline (1.0) > (-)-noradrenaline (0.39) > BRL 37344 (0.10). 5 Responses to BRL 37344 in the presence of prazosin (0.1 pM) and propranolol (1 pM) were antagonized by (±)-cyanopindolol (1pM), with a pKB of 6.56. Responses to isoprenaline, under the same conditions, were antagonized in a competitive manner by (±)-cyanopindolol (0.1-1 uM), with the slope of a Schild plot close to unity and a pA2 value of 7.44. 6 The resistance to blockade by prazosin and propranolol and the antagonism by cyanopindolol of the responses mediated by isoprenaline and BRL 37344 suggest that atypical f-adrenoceptors similar to 'atypical',f-adrenoceptors in rat adipocytes and other tissues are present in the rat gastric fundus.

show abstract

“…There is an ongoing debate as to whether UCP1 acts directly as a proton transporter, or as a fatty acid anion transporter where the free fatty acids function as cycling protonophores (3,4). A number of rat-selective ␤ 3 agonists have been discovered (2, 3,5,6) and shown to cause increases in metabolic rate, weight loss, and an improvement in glucose tolerance in dogs and rats (5)(6)(7)(8). The observed weight loss resulted from a decrease in body lipids with no decrease in muscle mass (8).…”

Section: Introductionmentioning

confidence: 99%

A selective human beta3 adrenergic receptor agonist increases metabolic rate in rhesus monkeys.

Fisher¹,

Amend²,

Bach³

et al. 1998

J. Clin. Invest.

111

View full text Add to dashboard Cite

Activation of ␤ 3 adrenergic receptors on the surface of adipocytes leads to increases in intracellular cAMP and stimulation of lipolysis. In brown adipose tissue, this serves to upregulate and activate the mitochondrial uncoupling protein 1, which mediates a proton conductance pathway that uncouples oxidative phosphorylation, leading to a net increase in energy expenditure. While chronic treatment with ␤ 3 agonists in nonprimate species leads to uncoupling protein 1 up-regulation and weight loss, the relevance of this mechanism to energy metabolism in primates, which have much lower levels of brown adipose tissue, has been questioned. With the discovery of L-755,507, a potent and selective partial agonist for both human and rhesus ␤ 3 receptors, we now demonstrate that acute exposure of rhesus monkeys to a ␤ 3 agonist elicits lipolysis and metabolic rate elevation, and that chronic exposure increases uncoupling protein 1 expression in rhesus brown adipose tissue. These data suggest a role for ␤ 3 agonists in the treatment of human obesity.

show abstract

Inhibition of rat colon motility by stimulation of atypical beta-adrenoceptors with new gut-specific agents

Cited by 31 publications

References 4 publications

Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the α‐ and β‐subtypes

Agonist and antagonist characterization of a putative adrenoceptor with distinct pharmacological properties from the α‐ and β‐subtypes

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

A selective human beta3 adrenergic receptor agonist increases metabolic rate in rhesus monkeys.

Contact Info

Product

Resources

About